Biomedical subjects

Yoshiro Niitsu

Publications and source records attributed to Yoshiro Niitsu.

At least 19 recordsLinked to original sources

PubMed2006

Clinical and endoscopic features of acute hemorrhagic rectal ulcer.

BACKGROUND: Acute hemorrhagic rectal ulcer (AHRU) has increasingly been reported in Japan, whereas it has rarely been reported in the English literature and is not yet established as a disease entity. The aim of this study was to elucidate clinical and endoscopic characteristics of patients with AHRU. METHODS: We enrolled 20 patients with 26 ulcers diagnosed as AHRU in our department between January 2001 and October 2005. Clinical features such as the underlying disorder, Karnofsky performance status (PS), and presence or absence of anticoagulant or antiplatelet therapy, as well as endoscopic findings and type of bleeding, were evaluated. Strategies for hemostasis were also reviewed. RESULTS: The most prevalent underlying disorder was diabetes mellitus, and the number of bedridden patients with PS 4 was relatively high. In addition, more than half of the patients had been treated with anticoagulant or antiplatelet agents. Endoscopically, ulcers were characteristically solitary and irregularly shaped, and they did not show any typical localization pattern. As a hemostatic strategy, clipping alone showed a favorable result, with a hemostatic success rate as high as 76.9%. CONCLUSIONS: This study may support the establishment of AHRU as a new clinical entity. In aged patients being treated with anticoagulant or antiplatelet agents, especially bedridden patients using aspirin, the possible appearance of this disease should be kept in mind.

Acute Disease↗

PubMed2006

Ex vivo large-scale generation of human platelets from cord blood CD34+ cells.

In the present investigation, we generated platelets (PLTs) from cord blood (CB) CD34(+) cells using a three-phase culture system. We first cultured 500 CB CD34(+) cells on telomerase gene-transduced human stromal cells (hTERT stroma) in serum-free medium supplemented with stem cell factor (SCF), Flt-3/Flk-2 ligand (FL), and thrombopoietin (TPO) for 14 days. We then transferred the cells to hTERT stroma and cultured for another 14 days with fresh medium containing interleukin-11 (IL-11) in addition to the original cytokine cocktail. Subsequently, we cultured the cells in a liquid culture medium containing SCF, FL, TPO, and IL-11 for another 5 days to recover PLT fractions from the supernatant, which were then gel-filtered to purify the PLTs. The calculated yield of PLTs from 1.0 unit of CB (5 x 10(6) CD34(+) cells) was 1.26 x 10(11) - 1.68 x 10(11) PLTs. These numbers of PLTs are equivalent to 2.5-3.4 units of random donor-derived PLTs or 2/5-6/10 of single-apheresis PLTs. The CB-derived PLTs exhibited features quite similar to those from peripheral blood in morphology, as revealed by electron micrographs, and in function, as revealed by fibrinogen/ADP aggregation, with the appearance of P-selectin and activated glycoprotein IIb-IIIa antigens. Thus, this culture system may be applicable for large-scale generation of PLTs for future clinical use.

Antigens, CD34↗

PubMed2006

Human herpesvirus-6 hepatitis associated with cyclosporine-A encephalitis after bone marrow transplantation for chronic myeloid leukemia.

A 31-year-old man referred to our hospital for treatment of his chronic myeloid leukemia (CML) in the first chronic phase by bone marrow transplantation. We pretreated him with cyclophosphamide and total body irradiation and bone marrow transplantation (BMT) was carried out. On day 31, the engraftment was confirmed and on day 52, acute graft versus host disease (GVHD) was observed. On day 189, he lost consciousness due to cyclosporine A-induced leukoencephalopathy and 375 mg cyclosporine A was changed to 100 mg prednisolone. On day 199, liver dysfunction (AST 410 IU/L, ALT 557 IU/L, gammaGTP 385 IU/L, ALP 363 IU/L, D-Bil 0.3 mg/dl) developed and a liver biopsy was performed. PCR analysis of DNA from the liver biopsy specimen was positive for HHV-6 and immunostaining using anti-HHV-6 and anti-HHV-6b antibodies showed positive staining in the cytosol of hepatocytes. No other viruses were found to induce hepatitis. From these results, he was diagnosed as having HHV-6 hepatitis and it was successfully treated with gancyclovir (GCV) administration.

Adult↗

PubMed2006

A phase I/II study of nedaplatin and 5-fluorouracil with concurrent radiotherapy in patients with esophageal cancer.

PURPOSE: To determine the recommended dose (RD) of cis-diammine-glycolatoplatinum (nedaplatin) when given concurrently with 5-FU and high dose radiation therapy in the treatment of esophageal cancer. The purpose of the phase II trial is to determine efficacy and further define the side effect profile. METHODS: Twenty-six patients with clinical stage I to IVA squamous cell carcinoma of the esophagus were enrolled in a non-surgical treatment comprised of a fixed dose of fluorouracil (400 mg/m2 administered as continuous intravenous infusion on days 1-5 and days 8-12) plus escalating doses of nedaplatin (40 mg/m2 in level 1, 50 mg/m2 in level 2, or 60 mg/m2 in level 3 on days 1 and 8), repeated twice every 3 weeks with concurrent radiotherapy (60 Gy). RESULTS: Between July 1998 and February 2004, a total of 26 patients entered this trial, all of whom were considered evaluable for toxicity assessment. In phase I of the study, 12 patients were treated in sequential cohorts of three to six patients per dose level. The maximum tolerated dose was reached at level 3 with two grade 4 neutropenia and one grade 4 thrombocytopenia. Thus, the recommended dosing schedule is level 2. Of the 20 patients treated at the RD level 2, including 6 patients of the RD phase I portion, 8 out of 20 patients (40%) had grade 3-4 neutropenia, 5 patients (25.0%) had grade 3-4 thrombocytopenia, 4 patients (20.0%) had grade 3 anemia and 4 patients (20.0%) had grade 3-4 esophagitis. Other toxicities were relatively mild and usually of grade 2 or less. Objective responses were noted in the 26 patients (overall response rate, 88.5%) including 11 (42.3%) complete remissions. The 1- and 3-year survival rates were 65.1 and 37.2%, respectively, with a median survival time of 21.2 months. CONCLUSIONS: The combination of nedaplatin and 5-FU with radiation is a feasible regimen that shows promising antitumor activity with an acceptable safety profile in patients with esophageal cancer.

Aged↗

PubMed2006

Colorectal cancer: genetics of development and metastasis.

It has been well documented that there are two major pathways in colorectal carcinogenesis. One is the chromosomal instability pathway (adenoma-carcinoma sequence), which is characterized by allelic losses on chromosome 5q (APC), 17p (p53), and 18q (DCC/SMAD4), and the other is a pathway that involves microsatellite instability. Recent progress in molecular biology, however, has shown that colorectal carcinogenesis is not necessarily clearly divided into these two pathways, but is in fact more complicated. Other routes, including the transforming growth factor-beta/SMAD pathway, the serrated pathway, and the epigenetic pathway, have been reported. Cross talk among these pathways has also been reported. In the invasion and metastasis steps of colorectal cancers, many more genes have now been identified as being involved in proteolysis, adhesion, angiogenesis, and cell growth. Recently accumulated evidence indicates that colorectal cancer is a genetically heterogeneous and complicated disease.

Adenocarcinoma↗

PubMed2006

Ex vivo expansion of G-CSF-mobilized peripheral blood CD133+ progenitor cells on coculture with human stromal cells.

OBJECTIVE: The pentaspan molecule CD133 has been shown to be a marker of more primitive hematopoietic progenitors in mobilized peripheral blood (PB). Our objective was to assess the efficacy of PB CD133(+) cells in our coculture system using human telomerized stromal (HTS) cells. METHODS: Five thousand PB CD133(+) cells or conventional cord blood (CB) CD34(+) cells were expanded with or without HTS cells in the presence or absence of stem cell factor, thrombopoietin, and Flk-2/Flt-3 ligand. RESULTS: The coculture was significantly superior in expanding PB clonogenic cells as compared with the stroma-free culture (CFU-C, 2 +/- 0 vs 111 +/- 15-fold of initial cell number, p < 0.01), and the fold increase of PB clonogenic cells was comparable to that for CB cells after two weeks of coculture (BFU-E, 54 +/- 3 vs 56 +/- 4-fold; CFU-GM, 156 +/- 26 vs 83 +/- 9-fold; CFU-Mix, 30 +/- 11 vs 80 +/- 36-fold). However, proliferation of CFU-Mk from PB on coculture with HTS cells was modest as compared with stroma-free culture. Concomitantly, multiple hematopoietic cells transmigrated below the stromal layer and formed cobblestone areas (CAs). The production of hematopoietic progenitor cells from CAs after coculture with PB was significantly lower than that seen in cells cocultured with CB for four weeks (CFU-Mix, 0 +/- 0 vs 9 +/- 5-fold on day 28, p < 0.01), although a similar number of CAs derived from PB and CB were observed. CONCLUSION: PB CD133(+) cells proliferated efficiently above the stromal layer, while the characteristics of PB CD133(+) cells underneath the human stromal layer were likely to be maintained, even after long-term hematopoietic-stromal interaction.

AC133 Antigen↗

PubMed2006

Amelioration of murine dextran sulfate sodium-induced colitis by ex vivo extracellular superoxide dismutase gene transfer.

BACKGROUND: Although the etiology of inflammatory bowel disease has not been fully clarified, reactive oxygen species is speculated to be involved. Extracellular superoxide dismutase (EC-SOD), an isozyme of SODs, is known to function mainly in body fluids. We investigated the efficacy of an ex vivo EC-SOD gene transfer into dextran sulfate sodium (DSS)-induced colitis mice. MATERIALS AND METHODS: Experimental colitis was induced by providing Balb/c mice with DSS in sterile distilled water provided as desired. The syngenic fibroblasts were obtained from Balb/c mice embryos and retrovirally transduced with the hEC-SOD gene. These engineered cells were confirmed to secrete EC-SOD in culture medium by enzyme-linked immunosorbent assay and were inoculated subcutaneously in the backs of DSS-treated mice. Mucosal injury of the colon was evaluated by the disease activity index (DAI: body weight, rectal bleeding, and stool consistency), grading of histologic disease severity, and levels of cytokine (tumor necrosis factor-alpha, interleukin-1beta) production. 8-Hydroxydeoxyguanosine (8-OHdG) levels in the mucosal tissue were assessed by immunohistochemical staining. Malondialdehyde (MDA) was measured using a colorimetric assay. RESULTS: A significant improvement was observed in DAI score and histologic severity as well as in mucosal tissue levels of inflammatory cytokines, 8-OHdG, and MDA of mice treated with the EC-SOD gene as compared with those without gene therapy, not only in a mild colitis model but also in a severe colitis model. Survival of treated mice in these models was significantly prolonged. CONCLUSIONS: Ex vivo transfer of the EC-SOD gene was feasible for treatment of DSS-induced colitis.

Animals↗

PubMed2006

[Effective combined modality therapy for a patient with primary adrenal lymphoma].

Primary adrenal lymphoma is a rare lymphoma with clinical features consisting of a high incidence of bilateral adrenal involvement, diffuse large B-cell histology and secondary adrenal insufficiency. We report a successful treatment of a patient with primary adrenal lymphoma using a combined modality therapy (CMT). A 62-year-old man was hospitalized with pain of the flank, and a computed tomography (CT) scan of the abdomen revealed very large, bilateral adrenal masses. A needle biopsy of the left adrenal mass revealed diffuse large B-cell lymphoma. After irradiation of both adrenal lymphomas and CHOP therapy accompanied by intrathecal treatment and rituximab, the patient underwent a left adrenalectomy and high-dose chemotherapy with autologous peripheral blood stem cell transplantation. The patient has been disease-free for 2 years after the diagnosis of primary adrenal lymphoma. In contrast to the previous reports of poor response to conventional-dose chemotherapy alone and short-term survival of patients with primary adrenal lymphoma, our patient has demonstrated that radiation therapy combined with chemotherapy and rituximab may be an effective modality as a first-line therapeutic regimen for localized primary adrenal lymphoma.

Adrenal Gland Neoplasms↗

PubMed2006

[De novo CD5-positive diffuse large B-cell lymphoma associated with autoimmune hemolytic anemia presenting as erythroid hypoplasia].

A 54-year-old woman was admitted due to high-grade fever, cervical lymphadenopathy and general malaise in May 2003. On examination, severe anemia was noted, direct Coombs and cold hemagglutinin tests were positive and the haptoglobin level was low in the peripheral blood. However, a bone marrow examination revealed marked erythroid hypoplasia. A diagnosis was made of co-existing combined type autoimmune hemolytic anemia (AIHA) and erythroid hypoplasia. A pathologic diagnosis of de novo CD5-positive diffuse large B-cell lymphoma (de novo CD5+ DLBCL) was made based on a cervical lymph node biopsy. The patient was treated with CHOP accompanied by rituximab (R-CHOP), resulting in complete remission after 3 courses of chemotherapy. The AIHA and erythroid hypoplasia subsided after 2 courses of R-CHOP. The sera obtained during erythroid hypoplasia significantly inhibited the growth of erythroid progenitor cells (erythroid colony-forming units, CFU-E) from her bone marrow collected after recovery. We report here a patient with de novo CD5+ DLBCL associated with both AIHA and erythroid hypoplasia, suggesting that the lymphoma triggered an abnormal immunity which generated some humoral inhibitors against erythropoiesis.

Anemia, Hemolytic, Autoimmune↗

PubMed2006

[Enteropathy-type T-cell lymphoma with CD8 and CD56 expression].

A 54-year-old male presented at a previous hospital with abdominal pain, where the patient was diagnosed as having abdominal and retroperitoneal lymphadenopathies by CT scan, then, he was referred to our hospital for further examination. Upper gastrointestinal endoscopy showed a tumor formation in the second portion of the duodenum, and there were medium sized atypical lymphocytes in biopsy specimens of the tumor. Since the atypical lymphocytes in the biopsy specimens were positive for CD3, CD8, CD56 and CD103 by immunostain, and had a rearrangement of the T-cell receptor 7-chain, the patient was diagnosed as having enteropathy-type T-cell lymphoma (ETL). Although ETL usually occurs as a complication of celiac disease, malabsorption and anti-gliadin antibodies, which are normally present in celiac disease, were not observed in this patient.

CD3 Complex↗

PubMed2006

[A case of recurrent biliary cystadenocarcinoma successfully treated with 5FU/CDDP systemic chemotherapy].

We report a case of biliary cystadenocarcinoma which recurred 41 months postoperatively. A 60-year-old woman was admitted for further examination of multiple metastatic tumors and a large amount of ascites. Systemic administration of 5FU and CDDP caused her CEA level to decrease gradually and abdominal computed tomography revealed considerable reduction of the metastatic tumors and ascites. Since her general condition had improved, chemotherapy was continued in the outpatient clinic.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2006

[Peripheral T-cell lymphoma presenting with eosinophilia due to interleukin-5 produced by lymphoma cells].

A 72-year-old male was admitted to our hospital to determine the cause of neck lymphadenopathies. He was diagnosed pathologically by a lymph node biopsy as having peripheral T-cell lymphoma (PTCL). He also had developed eosinophilia and his serum concentration of Interleukin-5 (IL-5) was extremely high. Immunostaining of a resected lymph node revealed that there were lymphoma cells which were stained with anti-IL-5 antibody. After 2 courses of CHOP therapy, the lymphadenopathies and eosinophilia disappeared and the concentration of serum IL-5 was normalized. It was suggested that IL-5 produced by lymphoma cells had induced his eosinophilia.

Aged↗

PubMed2006

[Anaphylactic reaction to oxaliplatin--a case of colon cancer].

Oxaliplatin (L-OHP) is a new third-generation platinum which is efficacious in treating advanced unresectable recurrent colorectal cancer as a first-line regimen. The marketing authorization was given in Japan in March, 2005. Its increased use has resulted in rare serious adverse effects, including anaphylactic shock. We experienced a case that developed anaphylactic shock by L-OHP. We report a 69-year-old man who was treated for recurrent colorectal cancer who underwent systemic chemotherapy with FOLFOX 4. After eight cycles he developed severe L-OHP associated neuropathy and lung metastases was a progressive tendency. The FOLFOX 4 regimen was discontinued and another modality, FOLFIRI regimen, was used. After eight cycles of FOLFIRI regimen, lung and liver metastases showed progressive disease for response assessment by RECIST criteria. Although a patient was stopped L-OHP for neurotoxicity, neuropathy was disappeared after 4 months interval. Therefore, we reintroduced L-OHP, FOLFOX 4 regimen. Anaphylactic shock occurred in the second cycle of reintroduction of the FOLFOX 4 regimen (total 10 cycles), 30 minutes after infusion of L-OHP. L-OHP infusion was immediately withdrawn and he was treated with intravenous hydroxyzine hydrochloride and methylprednisolone. The anaphylaxis symptoms resolved in 30 minutes. Chemotherapy based on L-OHP for unresectable recurrence colorectal cancer causes anaphylactic shock as a rare severe complication. The prediction factor is not proved. We should take steps for early detection of anaphylactic reaction and perform the appropriate treatment.

Adenocarcinoma↗

PubMed2005

Augmentation of antitumor effects of p53 gene therapy by combination with HDAC inhibitor.

We have previously shown that the HDAC inhibitors (HDACI) activate the p53 molecule through acetylation of 320 and 373 lysine residues, upregulate PIG3 and NOXA and induce apoptosis in cancer cells expressing wild and pseudo-wild type p53 genes (Terui T, et al. Cancer Res 2003; 63:8948-54). It has also been reported that expression of the Coxsackie adenovirus receptor and subsequent transfection efficiency of the adenovirus in cancer cells were enhanced by HDACI treatment. In this study, we extended these observations to explore the combination effect of adenoviral vector carrying wild type p53 (Ad-p53) gene therapy with a HDACI, sodium butyrate (SB), on xenografted human gastric cancer cells (KATO-III) and hepatocellular carcinoma cells (HuH7) in nude mice. We first confirmed an increased expression of Coxsackie adenovirus receptors with an associated increment of transgene (X-gal) expression by SB treatment in KATO-III cells. We then injected Ad-p53 into subcutaneous tumors of KATO-III and HuH7 combined with intraperitoneal administration of SB and found a significantly higher growth suppressive effect than single treatments of each. Even a complete regression of tumors was observed in three of five mice treated with this combination while with single treatment no tumor regression was observed. Tumors treated with the combination showed higher numbers of TUNEL positive cells than those treated with a single modality. Moreover, necrotic changes were more evident in tumors treated with the combination than separately, a compatible finding to the observation that vascularity revealed by CD34 staining was poorer in tumors treated with the combination than those treated with p53 gene or SB alone. This was further supported by the finding that BAI-1 (brain specific angiogenesis inhibitor-1), an inhibitor of vascularization, was induced by SB treatment in KATO-III and HuH7 cells transfected with Ad-p53. Thus SB was shown to be an efficient potentiator of p53 gene therapy for cancer.

Adenoviridae↗

PubMed2005

Human mesenchymal stem cells xenografted directly to rat liver are differentiated into human hepatocytes without fusion.

Hepatic transdifferentiation of bone marrow cells has been previously demonstrated by intravenous administration of donor cells, which may recirculate to the liver after undergoing proliferation and differentiation in the recipient's bone marrow. In the present study, to elucidate which cellular components of human bone marrow more potently differentiate into hepatocytes, we fractionated human bone marrow cells into mesenchymal stem cells (MSCs), CD34+ cells, and non-MSCs/CD34- cells and examined them by directly xenografting to allylalcohol (AA)-treated rat liver. Hepatocyte-like cells, as revealed by positive immunostaining for human-specific alpha-fetoprotein (AFP), albumin (Alb), cytokeratin 19 (CK19), cytokeratin 18 (CK18), and asialoglycoprotein receptor (AGPR), and by reverse transcription-polymerase chain reaction (RT-PCR) for expression of AFP and Alb mRNA, were observed only in recipient livers with MSC fractions. Cell fusion was not likely involved since both human and rat chromosomes were independently identified by fluorescence in situ hybridization (FISH). The differentiation appeared to follow the process of hepatic ontogeny, reprogramming of gene expression in the genome of MSCs, as evidenced by expression of the AFP gene at an early stage and the albumin gene at a later stage. In conclusion, we have demonstrated that MSCs are the most potent component in hepatic differentiation, as revealed by directly xenografting into rat livers.

Albumins↗

PubMed2005

Donor cell derived acute myeloid leukemia after allogeneic cord blood transplantation in a patient with adult T-cell lymphoma.

We report a patient with adult T-cell lymphoma who developed acute myeloid leukemia (AML) after allogeneic cord blood transplantation (CBT). Fluorescence in situ hybridization (FISH) studies and molecular analysis using short tandem repeat (STR) sequences proved the AML to be of donor origin. Although 25 cases of donor cell leukemia (DCL) occurring after allogeneic bone marrow transplantation have previously been reported, there have been no reports of DCL after CBT. This case is the first-reported DCL patient after CBT.

Acute Disease↗

PubMed2005

Cytomegalovirus cholangitis and pancreatitis in an immunocompetent patient.

Cholangitis and pancreatitis associated with cytomegalovirus (CMV) infection in an immunocompetent patient is reported. Endoscopic retrograde cholangiography performed on a 55-year-old man for evaluation of the cause of jaundice and liver dysfunction revealed a distal focal irregular narrowing of the common bile duct. Microscopic findings of the resected specimen showed chronic cholangitis and CMV pancreatitis. Immunohistochemistry disclosed that epithelial cells in the inflamed bile duct were positive for CMV antigen, which was compatible with CMV cholangitis. Inflammation of the biliary tract or pancreas by CMV has been commonly reported as a complication in immunocompromised patients. Our report appears to be a rare case, but suggests that CMV cholangitis or pancreatitis should be considered in the differential diagnoses of common bile duct stenosis or pancreatitis even in immunocompetent individuals.

Cholangitis↗

PubMed2005

A phase I/II study of S-1 plus cisplatin in patients with advanced gastric cancer: 2-week S-1 administration regimen.

BACKGROUND: The combination of a new oral dihydropyrimidine dehydrogenase-inhibitory fluoropyrimidine (S-1) and cisplatin (CDDP) is one of the most active chemotherapy regimens for gastric cancer. However, the optimum schedule for this combination has not yet been determined. This study was conducted to establish the maximum tolerated dose (MTD) and the recommended dose of CDDP when combined with 2-week S-1 administration, and to observe the safety and efficacy of the regimen as treatment for patients with advanced gastric cancer. METHODS: S-1 was administered orally at a dose of 80 mg/m2 per day for 2 weeks, followed by a 2-week rest. CDDP was administered intravenously on day 8 of each course; the initial dose of CDDP was 60 mg/m2 and it was increased in 10-mg/m2 increments. Treatment was repeated every 4 weeks unless disease progression was observed. RESULTS: Eleven patients were enrolled. The main toxicities were leucopenia, neutropenia, nausea, and anorexia. These toxicities were not severe, and were reversible and manageable. The MTD for CDDP was established as 80 mg/m2, as 2 of 5 (40%) patients developed dose-limiting toxicity (DLT) at this level. Therefore, the recommended dose of CDDP was determined to be 70 mg/m2. All 11 patients were evaluable for a response: 8 achieved a partial response and 1 had stable disease. The overall response rate was 73%. CONCLUSION: This regimen is considered to be generally well-tolerated and has substantial antitumor activity.

Administration, Oral↗