Search PubMed⌕ Search

Biomedical subjects

Yoshiro Niitsu

Publications and source records attributed to Yoshiro Niitsu.

At least 91 records · Page 5Linked to original sources
PubMed2003

Allogeneic bone marrow transplantation in a patient with T-prolymphocytic leukemia with small-intestinal involvement.

Although T-prolymphocytic leukemia (T-PLL) is characterized by organ infiltration, small-intestinal involvement is rare. We performed an unrelated allogeneic bone marrow transplantation in a patient with T-PLL who had multiple lymphomatous polyposis of the small intestine refractory to combination chemotherapy (cyclophosphamide, vincristine, and prednisolone [COP] and fludarabine plus cyclophosphamide). The patient developed no graft-versus-host disease (GVHD) and remains in complete remission 16 months after the transplantation. T-PLL is usually refractory to chemotherapy and is a T-cell malignancy with poor prognosis. There have been several reports on allogeneic hematopoietic stem-cell transplantation (allo-HSCT) for T-PLL, but none on allo-HSCT for T-PLL patients with intestinal involvement. It is suggested that allo-HSCT may improve the prognosis in patients with T-PLL involving the small intestine.

Adult↗
PubMed2003

Telomerized human multipotent mesenchymal cells can differentiate into hematopoietic and cobblestone area-supporting cells.

OBJECTIVE: To compare the hematopoietic support provided by telomerized human mesenchymal stem cells (MSCs) and telomerized MSC-derived stromal cells. METHODS: We transfected the human telomerase catalytic subunit (hTERT) gene into primary MSCs to establish hTERT-transduced MSCs (hTERT-MSCs). Stromal induction of hTERT-MSCs was performed by replacing the culture medium with Dexter-type culture medium. Hematopoietic support was examined by coculture with cord blood CD34(+) cells. RESULTS: The hTERT-MSCs were morphologically identical with the primary MSCs and expressed surface antigens including CD105, CD73, and CD166. hTERT-MSCs showed a similar doubling time as primary MSCs and continued to proliferate to over 80 population doublings (PD), although the primary MSCs underwent crisis in vitro at 16 PD. The osteogenic, chondrogenic, adipogenic, neurogenic, and stromal differentiation potential of hTERT-MSCs were maintained up to at least 40 PD. The degree of expansion of CD34(+) cells and total number of colony-forming units in culture (CFU-C) upon 12-day coculture with the hTERT-MSC-derived stromal cells were nearly the same as those upon 12-day coculture with hTERT-MSCs (CD34, 33.0-fold+/-2.8-fold vs 36.1-fold+/-1.7-fold of the initial cell number; CFUs, 344.4-fold+/-62.5-fold vs 239.3-fold+/-87.0-fold; CFU-mix, 368.4-fold+/-113.7-fold vs 341.3-fold+/-234.3-fold). However, on day 18 of coculture, the number of cobblestone areas (CA) observed beneath the stromal cells was 15 times higher than that beneath hTERT-MSCs (CA, 146.9+/-54.6 vs 9.4+/-8.1, p<0.01). CONCLUSION: Stromal induction of hTERT-MSCs exclusively enhanced the support of CA formation provided by hTERT-MSCs. Our human hTERT-MSCs will be useful for elucidating the mechanism of the formation of CAs.

Adult↗
PubMed2003

Ethanol induces transforming growth factor-alpha expression in hepatocytes, leading to stimulation of collagen synthesis by hepatic stellate cells.

BACKGROUND: Liver fibrosis often develops in alcoholic liver diseases without accompanying inflammation; however, the underlying mechanism is unclear. Using ethanol-exposed human HepG2 hepatoblastoma cells as a model for alcoholic liver diseases, we previously found that ethanol exposure causes HepG2 cells to secrete an approximately 6,000 Da nonheparin-binding polypeptide that stimulates collagen synthesis in human IMR-90 fibroblasts. The aim of the current study was to characterize and identify this factor. METHODS: Concentration of type I procollagen peptide and transforming growth factor (TGF)-alpha was assessed by enzyme-linked immunosorbent assay. TGF-alpha protein expression was examined by Western blot. Type I collagen messenger RNA expression in rat hepatic stellate cells was assessed by reverse transcription-polymerase chain reaction. RESULTS: The collagen-stimulating activity in conditioned media from ethanol-exposed HepG2 cells to stimulate type I procollagen peptide synthesis of IMR-90 cells was specifically inhibited by addition of anti-TGF-alpha antibodies. Western blot analysis showed increased TGF-alpha protein expression in ethanol-treated HepG2 cells. TGF-alpha in conditioned medium from ethanol-exposed HepG2 cells stimulated type-I collagen messenger RNA expression in rat hepatic stellate cells. CONCLUSIONS: These results suggest that TGF-alpha derived from ethanol-exposed hepatocytes may contribute to the development of hepatic fibrosis in alcoholic liver diseases.

Blotting, Western↗
PubMed2003

[Successful treatment after acute promyelocytic leukemia (APL) syndrome of relapsed API with arsenic trioxide].

A 52-year-old female was diagnosed with relapsed APL in 2000. After obtaining informed consent, we administered 10 mg/day of arsenic trioxide intravenously. The complications were vomiting, increased transaminase and ATRA syndrome which included high fever, retention of body fluid, pleural effusion, pericardial effusion and respiratory failure from day 16. Administration of steroid and low dose chemotherapy (DNR 60 mg x day 1-2, BH-AC 250 mg x day 1-2) with arsenic was effective for APL syndrome, and complete remission (CR) was obtained at day 35 and PML-RAR mRNA became negative. After obtaining CR, consolidation chemotherapy was conducted and the patient was maintained the CR for more than 18 months. Although arsenic trioxide may be effective for relapsed APL, sufficient caution is needed because of the possibility of various complications.

Antineoplastic Agents↗
PubMed2003

[Helicobacter pylori infection and idiopathic thrombocytopenic purpura].

The prevalence of Helicobacter pylori(H. pylori) infection and the effect of its eradication on platelet count in 51 chronic idiopathic thrombocytopenic purpura(ITP) and 9 secondary autoimmune thrombocytopenic purpura(SAITP) patients, were investigated. H. pylori infection was found in 31 ITP patients(60.8%) and in two SAITP(22.2%). H. pylori eradication was obtained in 24 of 26 infected ITP patients. 14 of 24 H. pylori-eradicated patients(58.3%) showed a significant increase in platelet count 6 months after eradication, however two infected patients with SAITP did not show platelet increase. This response was maintained in all responding patients throughout the follow-up period(median 20 months).

Female↗
PubMed2003

[A case of irinotecan-resistant colon cancer responding to chronotherapy with oxaliplatin, 5-FU, l-LV].

We report a case of irinotecan-resistant colon cancer responding to chronotherapy with oxaliplatin (L-OHP), 5-FU, l-LV (l-Leucovorin). A 72-year-old man was examined at a certain hospital because of constipation and appetite loss. Chest computed tomography (CT) revealed lung metastases, and abdominal CT revealed liver metastases. He was then referred to our hospital. A colonoscopy revealed type 2 tumor in the colon, at the hepatic flexure. We diagnosed adenocarcinoma of the colon with metastases to the liver and lung. Resection of the primary lesion was performed, and chemotherapy consisting of systemic administration of CPT-11, 5-FU and l-LV was performed. After 2 courses of combined treatment with CPT-11/5-FU/l-LV, CT revealed considerable reduction of the metastatic tumors. However, after 3 courses of combined treatment, progressive disease was observed and new brain and bone metastases were detected. We imported and used a non-approved/pending drug, oxaliplatin from the Remedy and Health Corporation, with informed consent from the patient and his family and our clinical ethics committee. Chronotherapeutic schedules have been performed, from which the safety and activity of oxaliplatin against advanced colorectal cancer was reported. Our patient received a 5-day course of chronomodulated 5-FU and l-LV (750 and 300 mg/body/day, respectively; peak delivery rate at AM 4:00 hours) with L-OHP on the first day of each course (100 mg/body, as a 6-hour infusion). Each course was again repeated every 21 days. A partial response was observed in the liver and lung metastases. These results indicate that chronomodulated 5-FU and LV with L-OHP therapy could be an effective regimen for cases of irinotecan-resistant colon cancer.

Aged↗
PubMed2003

[A case responding to weekly paclitaxel (TXL) therapy as third line chemotherapy for scirrhous type gastric cancer].

A 67-year-old female was admitted to our hospital in May, 2001 for examination. She was diagnosed with advanced gastric cancer that was inoperable due to peritoneal dissemination. Seventeen courses of sequential MTX and 5-FU therapy, and 2 courses of TS-1 plus CDDP were carried out. A partial response (PR) and prolonged NC were obtained after these chemotherapies. However, pleural effusion and ascites appeared again, and we diagnosed progressive disease. As a third line chemotherapy for this patient, paclitaxel (TXL) was administered. Treatment consisted of two 3-week courses of paclitaxel 70 mg per m2 on day 1 of each week, with a 1-week break between the courses. Two weeks after the start of this therapy, pleural effusion and ascites had completely disappeared. Paclitaxel is considered to be promising for advanced gastric cancers, as second or third line chemotherapy with paclitaxel for patients with inoperable gastric cancer seems to be effective in improving QOL.

Adenocarcinoma, Scirrhous↗
PubMed2003

[Successful induction and long-term molecular remission with imatinib mesylate and chemotherapy in a case of Ph-positive acute lymphoblastic leukemia].

The patient was a 68-year-old woman who was diagnosed as having Ph-positive acute lymphoblastic leukemia (ALL). Complete remission (CR) was not obtained with the induction therapy of the Japan Adult Leukemia Study Group Protocol. We then considered administration of imatinib (ST1571). The institutional review board of our hospital approved this therapy, and we initiated the administration of imatinib 400 mg/day after obtaining written informed consent from the patient. At day 10 of the regimen, CR was achieved, treatment had to be discontinued RT-PCR showed no induction of detectable minor bcr-abl mRNA after three courses of consolidation chemotherapy combined with imatinib. We changed the administration protocol of Imatinib to two weeks out of every in four, weeks, and conducted 9 courses of consolidation chemotherapy. The negative result of RT-PCR has been maintained 10 months after diagnosis. The adverse effects were body weight gain and retaining pleural effusion, and these were controlled by the diuretics. The negative result of RT-PCR in Ph positive ALL after chemotherapy has rarely been reported, so the combination of imatinib and chemotherapy may be considered to be effective for Ph positive ALL.

Aged↗
PubMed2003

[Chemotherapy with ubenimex corresponding to patient age and organ disorder for 18 cases of acute myelogeneous leukemia in elderly patients--effects, complications and long-term survival].

Ubenimex was concurrently administered to 18 elderly patients with acute myelocytic leukemia (AML), and a chemotherapy protocol was prepared corresponding to patient age and organ disorders. The dose-reduced protocol of the Japan Adult Leukemia Study Group (JALSG) '95 or aclarubicin 14 mg/m2 day 1-4, cytosine arabinoside 15 mg/m2 day 1-14, granulocyte colony stimulating factor (G-CSF) 150 micrograms/body day 1-14 (CAG therapy) were administered. In addition, ubenimex 30 mg/day was administered orally after induction of remission. As per the JALSG protocol for dose reduction when organ disorder is absent, 85% and 70% of the dose were administered to the patients aged 65-69 years and 70-74 years, respectively. For patients aged 75 years or more and patients with mild disorders of the heart, kidney, and liver, CAG therapy was administered. As a result, the complete remission (CR) rate was 67%, and the three-year survival rate was 32%. This protocol may be useful for elderly AML.

Aclarubicin↗
PubMed2003

[IgM type multiple myeloma expressing various surface adhesion molecules and demonstrating an aggressive clinical course].

A 70-year-old woman was admitted for anemia, elevated serum total protein and a right axillary mass. Laboratory data showed monoclonal x IgM with a decrease in serum IgG and IgA levels. An occipital punched-out lesion was detected on a cranial X-ray. A tumor lesion was detected on chest X-ray and computed tomography. Biopsy specimen revealed plasmacytoma with cytoplasmic IgM. Bone marrow aspiration revealed an elevated plasma cell count. An immunophenotype analysis of the plasma cells showed positivity of cytoplasmic IgM, x, CD5, CD38, CD11a (LFA-1), CD44 (HCAM), CD49d (VLA-4) and CD54 (ICAM-1). From the above results, we diagnosed the patient as having IgM myeloma associated with plasmacytoma. Melphalan and prednisolone therapy were prescribed, their effect on the myeloma was short term, so we changed the chemotherapy to VAD (vincristine, adriamycin and dexamethasone), but this treatment had little effect. The patient developed bacterial pneumonia and died. IgM myeloma is a rare disease and reports of immunophenotype analysis are also rare. There is no case report of plasmacytoma associated with IgM myeloma.

Aged↗
PubMed2002

Ex vivo expansion of human umbilical cord hematopoietic progenitor cells using a coculture system with human telomerase catalytic subunit (hTERT)-transfected human stromal cells.

We developed a new human stromal cell line that could expand human hematopoietic progenitor/stem cells. Primary human bone marrow stromal cells were infected with retrovirus containing the human telomerase catalytic subunit (hTERT) gene, resulting in increased population doubling and the acquisition of cell immortalization. Characteristics of the hTERT-transduced stromal (hTERT-stromal) cells were identical with those of the primary stromal cells in terms of morphologic appearance and expression of surface antigens. Human cord blood (CB) CD34(+) cells were expanded by coculture with primary stromal or hTERT-stromal cells in the presence of stem cell factor, thrombopoietin, and Flk-2/Flt-3 ligand under serum-free condition. The degree of expansion of CD34(+) cells and total number of colony-forming units in culture (CFU-Cs) after 2 weeks' coculture with the hTERT-stromal cells were nearly the same as those after 2 weeks' coculture with primary stromal cells (CD34(+) cells, 118-fold +/- 8-fold versus 117-fold +/- 13-fold; CFU-Cs, 71-fold +/- 5-fold versus 67-fold +/- 5-fold of initial cell number). CB expansion on hTERT-stromal cells occurred at a similar rate through 7 weeks. In contrast, the rate of CB expansion on primary stromal cells had drastically declined at 7 weeks. In nonobese diabetic/severe combined immunodeficiency (SCID) mice, the degree of engraftment of SCID-repopulating cells that had been cocultured with hTERT-stromal cells for 4 weeks was significantly higher than that of precocultured CB cells. These results indicate that this hTERT-stromal cell line could be useful for ex vivo expansion of hematopoietic progenitor/stem cells and for analyzing the microenvironment of human bone marrow.

Animals↗
PubMed2002

Induction of heat shock protein 47 synthesis by TGF-beta and IL-1 beta via enhancement of the heat shock element binding activity of heat shock transcription factor 1.

With most immunological reactions, tissue fibrosis, collagen overproduction caused by immune cytokines, is inevitably associated. Among the various immune cytokines, heat shock protein 47 (HSP47) is a procollagen-specific molecular chaperon and is essential for secretion of procollagen from cells. Induction of HSP47 by TGF-beta has been previously reported in rat skeletal myoblasts and mouse osteoblasts, but not in human diploid fibroblasts. As for IL-1beta, its effect on HSP47 has not been elucidated. In the present study, using human embryonic lung fibroblast cells, we first disclosed that both TGF-beta and IL-1beta induced HSP47 synthesis. We then revealed that the binding of the heat shock element (HSE) by heat shock transcription factor 1 (HSF1) was enhanced by both cytokines. We further demonstrated that trimer formation of HSF1, which is essential for its binding to HSE, was induced by these cytokines. The enhancement of HSP47 synthesis and their trimer formation of HSF1 were augmented by using a combination of both cytokines. Collectively, TGF- beta and IL-1beta were found to induce trimer formation of HSF1 which in turn bound to HSE of HSP47, resulting in the enhancement of HSP47 expression. Thus, HSP47 could well be a good candidate for molecular targeting in controlling tissue fibrosis, given that both principal fibrinogenetic cytokines (TGF-beta, IL-1beta) are commonly involved in its induction through HSF1 trimerization.

Cell Line↗