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Junji Kato

Publications and source records attributed to Junji Kato.

At least 55 records · Page 3Linked to original sources
PubMed2004

Recovery of neutrophil count by ganciclovir in patients with chronic idiopathic neutropenia associated with cytomegalovirus infection in bone marrow stromal cells.

Patients with chronic idiopathic neutropenia (CIN) usually show chronic inflammation in their bone marrow stromal cells, but the etiologies of this disorder are still unknown. We suspected viral infection of the bone marrow stromal cells and used polymerase chain reaction (PCR) analysis to test for cytomegalovirus (CMV) infection in 4 patients with CIN and in 6 healthy volunteers. Peripheral blood mononuclear cells did not yield signals in any of the patients or healthy volunteers, but PCR analysis for CMV DNA in bone marrow stromal cells showed positive signals in 2 of the patients with CIN. CMV DNA was not detected in the other 2 patients or in the healthy volunteers. The 2 patients who were positive for stromal CMV received 500 mg/day ganciclovir for 14 days. After this treatment, the PCR band showing the presence of stromal CMV disappeared, and the neutrophil numbers of the 2 patients who received this viral eradication therapy normalized 6 months after treatment. In conclusion, the etiology in some cases of CIN is speculated to be infection by CMV in bone marrow stromal cells, and treatment with ganciclovir may be effective in treating such patients.

Aged↗
PubMed2004

[A case report of unresectable gastric cancer that responded to 5-FU plus paclitaxel (FT) therapy].

We report a case of a 63-year-old man who has been treated by FT therapy (5-fluorouracil (5-FU) plus paclitaxel therapy). The regimen includes 600 mg/m2/day of 5-FU by continuous i.v. administration from day 1 to 5 and consequent administration of paclitaxel (90 mg/m2/day) on days 8, 15, and 22 for 28 days repetitively. Before the therapy was started, that occurred were obstructive jaundice, ascites, and poor performance status due to gastric cancer were observed. After percutaneous transhepatic drainage was performed, the patient was started on the above-mentioned regimen even before full recovery from the hepatic dysfunction. As the treatment proceeded, he showed good response (ascites disappeared and the size of swollen perigastric lymph node was reduced, which were confirmed as a partial response by sequential CT examination) to the therapy and his QOL and PS also improved. He has continued to receive this regimen for over 1 year and 4 months without any sign of progressive disease by CT examination. No adverse event greater than grade 1 by the NCI-CTC criteria was seen, except for alopecia (grade 2). Considering the favorable response and mild toxicity, this regimen is useful even for the patients with poor performance status and severe hepatic dysfunction.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2004

[Successful treatment with antiviral agents for human herpesvirus type 6 encephalitis following reduced intensity stem cell transplantation in a patient with myelodysplastic syndrome].

We report here a patient who suffered from PCR-confirmed human herpesvirus type 6 (HHV-6) encephalitis following reduced intensity stem cell transplantation (RIST) from her HLA-matched sibling donor. A 66-year-old woman with MDS-RA underwent RIST from her HLA-matched brother. Engraftment was favorable and grade 2 GVHD (skin and intestine) was observed with good response to 60 mg of prednisolone. On day 162, she developed fever, headache, diplopia, disorientation and abnormal neurological findings including cervical stiffness and nystagmus. An analysis of cerebrospinal fluid (CSF) revealed 80 cells/microl, a glucose level of 50 mg/dl and a protein level of 97 mg/dl on day 162. Although computed tomography (CT) of the brain and electroencephalography (EEG) were nonspecific, HHV-6 was detected in the CSF using polymerase chain reaction (PCR) techniques and the patient was diagnosed as having encephalitis due to local reactivation of HHV-6. Administration of ganciclovir (GCV) and acyclovir (ACV) were started from day 162. Treatment with antiviral agents was effective, with total resolution of her symptoms and the DNA of this virus disappeared from the CSF after 23 days of treatment. This case shows that HHV-6 infection has to be considered in patients with neurological symptoms following stem cell transplantation, and suggests the necessity of PCR for HHV-6 virus from the CSF.

Acyclovir↗
PubMed2004

[A case of metastatic liver tumor from colorectal carcinoma--continued arterial infusion chemotherapy through a microcatheter located in replaced right hepatic artery].

The patient was a 78-year-old male with a history of colon cancer. After surgical resection of colon cancer, he suffered a multiple liver metastasis. We treated him by arterial infusion chemotherapy with the catheter edge embedded at the common hepatic artery. For a long period, the lesions were defined as partial response on WHO-criteria, but a wide area of the common hepatic artery was shrunk. After changing the treatment to systemic intravenous chemotherapy, the metastatic lesions began to enlarge. Then, we somehow were able to put a microcatheter into the replaced right hepatic artery (rRHA), and could restart arterial infusion chemotherapy. We continued this procedure for over a year without any complication.

Adenocarcinoma↗
PubMed2004

[Ferritin].

Explore the source record for details and available documents.

Female↗
PubMed2003

Induction of PIG3 and NOXA through acetylation of p53 at 320 and 373 lysine residues as a mechanism for apoptotic cell death by histone deacetylase inhibitors.

Two controversial issues regarding p53 are whether it is involved in apoptosis induction of tumor cells by a histone deacetylase (HDAC) inhibitor and, given that p53 is indeed involved, which genes of acetylated p53 targets are responsible for giving rise to apoptotic death. We, in the present study, first confirmed that some substantial extent of apoptotic cell death was seen when p53-deficient cells (KATO-III) were transfected with wild-type p53 and treated with sodium butyrate (SB) or trichostatin A. By Western blotting, using specific antibodies, we then demonstrated that residues 320, 373, and 382 lysines of p53 were acetylated in KATO-III cells transfected with wild-type p53 (KATO-III/p53) treated with a HDAC inhibitor. However, as revealed by terminal deoxynucleotidyl transferase-mediated nick end labeling staining, only those KATO-III cells transfected with K320R p53 or K373R p53 became insensitive to the HDAC inhibitor, suggesting that these two residues of p53 may be essential for HDAC inhibitor-induced apoptosis, whereas others such as K382R p53 may not. Furthermore, reverse transcription-PCR demonstrated that among various p53-related proapoptotic genes, expression of PIG3 and NOXA were clearly enhanced by SB treatment in KATO-III/p53 cells but not in KATO-III/K320R or KATO-III/K373R cells. Finally, we revealed that apoptosis could be evoked by SB even in cells where p53 mutations occur at residues other than 320 lysine or 373 lysine (TMK-1 and HSC-39 cells) and that this apoptosis was significantly, although not totally, suppressed by the anti-p53 antisense. It was, therefore, concluded that acetylation of the p53 molecule at residues 320 and 373, giving rise to up-regulation of PIG3 and NOXA, is one of the mechanisms for induction of apoptosis by HDAC inhibitors in cancer cells.

Acetylation↗
PubMed2003

Increased expression of angiogenin in hepatocellular carcinoma in correlation with tumor vascularity.

PURPOSE: Neovascularization is known to be one of the major characteristics of human hepatocellular carcinoma (HCC). Angiogenin (ANG), originally discovered in a human colon cancer cell line, is a liver-derived polypeptide that shows strong angiogenic activity in vivo. However, the role of ANG on the development of HCC remains unknown. The present study was designed to examine the implication of ANG in the neovascularization of human HCC. EXPERIMENTAL DESIGN: Forty-one HCC patients who had undergone conventional celiac angiography were used in this study. ANG protein expression and microvessel density (MVD) in HCC specimens obtained by liver biopsy or surgical resection were examined by immunohistochemistry, and the levels were quantified by the KS-400 image analyzing system. ANG mRNA expression in liver tissues was evaluated by in situ hybridization. Serum ANG concentrations were measured by an ELISA. Survival rates were calculated using the Kaplan-Meier method. RESULTS: Immunohistochemistry and in situ hybridization showed greater increments of ANG protein expression and mRNA expression, respectively, in HCC tissues than in the surrounding nontumorous tissues. MVD within tumorous tissues increased according to dedifferentiation of the histological grade of HCC, showing a significant correlation (r = 0.877, P = 0.0009) with ANG expression levels. Mean +/- SD serum ANG levels of healthy subjects and chronic hepatitis (CH) patients were 362.3 +/- 84.1 ng/ml and 331.9 +/- 133.8 ng/ml, respectively, with no significant difference. Serum ANG levels of liver cirrhosis patients (242.4 +/- 126.9 ng/ml) were lower than those of healthy subjects or CH patients and decreased as the fibrosis grade advanced. In HCC patients, despite the cirrhotic background, serum ANG levels increased as the tumor vascularity increased (197.8 +/- 64.9 ng/ml for hypovascular, 326.7 +/- 148.6 ng/ml for hypervascular, and 405.0 +/- 121.3 ng/ml for very hypervascular), in good accordance with histological grading, and significantly decreased (P = 0.015) after successful treatment with transcatheter arterial embolization or percutaneous ethanol injection. HCC patients were conventionally divided into two groups according to the serum level of ANG, those with values higher than the mean level (332.9 +/- 143.8 ng/ml) and those with values lower than the mean,; the 5-year survival rate of the latter group was determined to be significantly higher than that in the former group. CONCLUSIONS: These results suggest that ANG is one of the neovascularization defining factors of HCC. Thus, measuring serum ANG may assist in monitoring the disease, and targeting ANG may provide a new strategy for treating advanced HCC.

Adult↗
PubMed2003

Interaction between leukemic-cell VLA-4 and stromal fibronectin is a decisive factor for minimal residual disease of acute myelogenous leukemia.

Bone-marrow minimal residual disease (MRD) causes relapse after chemotherapy in patients with acute myelogenous leukemia (AML). We postulate that the drug resistance is induced by the attachment of very late antigen (VLA)-4 on leukemic cells to fibronectin on bone-marrow stromal cells. We found that VLA-4-positive cells acquired resistance to anoikis (loss of anchorage) or drug-induced apoptosis through the phosphatidylinositol-3-kinase (PI-3K)/AKT/Bcl-2 signaling pathway, which is activated by the interaction of VLA-4 and fibronectin. This resistance was negated by VLA-4-specific antibodies. In a mouse model of MRD, we achieved a 100% survival rate by combining VLA-4-specific antibodies and cytosine arabinoside (AraC), whereas AraC alone prolonged survival only slightly. In addition, overall survival at 5 years was 100% for 10 VLA-4-negative patients and 44.4% for 15 VLA-4-positive patients. Thus, the interaction between VLA-4 on leukemic cells and fibronectin on stromal cells may be crucial in bone marrow MRD and AML prognosis.

Animals↗
PubMed2003

Reversal of multiple drug resistance in cholangiocarcinoma by the glutathione S-transferase-pi-specific inhibitor O1-hexadecyl-gamma-glutamyl-S-benzylcysteinyl-D-phenylglycine ethylester.

Cholangiocarcinoma is markedly resistant to chemotherapy and has a dismal prognosis, but its mechanism of drug resistance is unknown. This study examines whether glutathione S-transferase-pi (GSTP1-1) is involved in resistance to anticancer drugs in cholangiocarcinoma and whether GSTP1-1-specific inhibitors can overcome this resistance. First, immunohistochemical examination disclosed strong staining of all our 17 cholangiocarcinoma specimens for GSTP1-1, irrespective of histological type. Transfection of the GSTP1-1 antisense expression vector into a human cholangiocarcinoma cell line (HuCCT1) apparently decreased its intracellular GSTP1-1 concentration, and the sensitivity of transfectants to adriamycin (ADR), cisplatin, and alkylating agents such as melphalan and 4-hydroxyperoxycyclophosphamide (4-HC) was increased significantly, compared with that of mock transfectants. We next synthesized GSTP1-1-specific inhibitors by elongating the carbon chain of the ethylester at the N-terminal of gamma-glutamyl-S-benzylcysteinyl-phenylglycyl diethylester and performed a pharmacokinetic study on them. Of six GSTP1-1 inhibitors tested, O1-hexadecyl-gamma-glutamyl-S-benzylcysteinyl-d-phenylglycine ethylester (C16C2) showed the smallest volume of central compartment and smallest volume of distribution at steady state and the second smallest clearance, being the most effective inhibitor in vivo. The IC50 value of ADR or 4-HC for HuCCT1 cells decreased greater by treatment with C16C2 in a dose-dependent manner, paralleling the decrease in GSTP1-1 activity, than that of ADR or 4-HC alone. The antitumor activity of ADR or cyclophosphamide was clearly enhanced by combination therapy with C16C2 in a xenograft model. In conclusion, our results demonstrated that GSTP1-1 is a resistance factor for anticancer drugs in cholangiocarcinoma and that C16C2, a GSTP1-1-specific inhibitor, is a potent agent against the resistance.

Animals↗
PubMed2003

Thrombopoietin concentrations in peripheral blood correlated with platelet numbers in two patients with thrombocytopenia by chronic graft-versus-host disease.

Thrombocytopenia is well known to be one of the clinical manifestations of chronic graft-versus-host disease (cGVHD). However, there exist cases in which the cause of thrombocytopenia has been unexplained. Recently, thrombopoietin (TPO) from bone marrow (BM) stromal cells and transforming growth factor (TGF)-beta from platelets and megakaryocytes have been identified as strong positive and negative regulators of megakaryopoiesis in vivo. We hypothesized that the decreased TPO production from BM could be one of the causes of thrombocytopenia in the patients with cGVHD. In the present study, therefore, TPO and TGF-beta concentrations in peripheral blood (PB) and BM were measured serially in two patients with acute leukemia who had received fully matched stem cell transplantation from relatives and subsequently developed extensive cGVHD with thrombocytopenia. The results showed that platelet numbers correlated well with the TPO concentrations, which were consistently higher in BM than in PB. The difference in TPO concentrations between BM and PB was decreased when the platelet levels were low, indicating that the amount of TPO production from BM decreased throughout the duration of thrombocytopenia. TGF-beta concentrations were normal during all periods in which measurements were carried out. Thus, our results suggest that one mechanism of thrombocytopenia in patients with cGVHD is low TPO production by BM cells.

Adult↗
PubMed2003

Inhibition of type I procollagen production by tRNAVal CTE-HSP47 ribozyme.

BACKGROUND: Fibrosis characteristically occurs in the advanced stages of chronic inflammatory diseases, occasionally as the primary lesion, and frequently determines the disease prognosis. Fibrotic lesions consist mostly of collagen, and therefore it may be possible to prevent or treat fibrosis by inhibiting collagen production. Of the currently available therapeutic approaches, however, none is sufficiently effective and specific for inhibition of collagen. Heat shock protein 47 (HSP47) is a collagen-specific molecular chaperone that has been reported to play a pivotal role in secretion of procollagen molecules. Therefore, we have tried to suppress its function to inhibit these various types of collagen. METHODS: We have developed a novel type of ribozyme by ligating a hammerhead sequence to a tRNA(Val) promoter to facilitate displacing the ribozyme from nucleus to cytoplasm and to constitutive transport element, a binding motif of helicase which unwinds mRNA to render the target sequence on the mRNA accessible to the ribozyme. RESULTS: The ribozyme thus constructed showed strong activity to cleave HSP47 mRNA and suppress the secretion of type I procollagen in the human primary fibroblast. CONCLUSION: We suggest applicability of this ribozyme as a new modality for antifibrosis therapy.

Antisense Elements (Genetics)↗
PubMed2003

Fatality caused by self-bloodletting in a patient with factitious anemia.

Death by bloodletting among patients with factitious anemia has never been reported to our knowledge. We report the first known case. A 25-year-old woman with severe iron deficiency anemia confessed her habit of bloodletting at her first visit to our hospital, in March 1998. We prescribed oral iron and referred her to a psychiatrist. The diagnosis was borderline personality disorder. The psychiatrist began counseling the patient and prescribed a major tranquilizer. The patient's method of bloodletting was to insert an 18-gauge needle without syringe into her vein after inducing congestion in her arm. This method was considered to involve risk of death, because once the patient fell into a faint caused by blood loss, the bloodletting could not be stopped. Although we attempted to persuade the patient to stop bloodletting by this method, she died after self-bloodletting in September 1999. It is not known whether the death was intentional suicide or an accident.

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

Clinical application of Er:YAG laser for cavity preparation in children.

OBJECTIVE: The purpose of this study was to determine the clinical usefulness of Er:YAG laser for cavity preparation in children. BACKGROUND DATA: The conventional methods for cavity preparation instill fear and discomfort in pediatric patients. The Er:YAG laser is a new tool developed for cavity preparation; however, there are few reports of its clinical application. MATERIALS AND METHODS: A clinical evaluation using an Er:YAG laser was carried out using 32 subjects (with 16 deciduous and 19 permanent teeth) with ages ranging from 2 to 12 years. All cavities were restored with light-cured composite resin following the application of bonding agent, but without acid etching or primer conditioning. RESULTS: During laser treatment, the pediatric patients were very cooperative and hardly complained of any pain, and no tooth showed undesirable effects during the 3-year period of observation. CONCLUSION: It can be concluded from the results of this study that an Er:YAG laser would be a useful alternative method for cavity preparation for composite resin restoration in children.

Acrylic Resins↗
PubMed2003

Prevention of dental caries in partially erupted permanent teeth with a CO2 laser.

OBJECTIVE: The purpose of this study was to determine the effect of CO2 laser irradiation in the prevention of pit and fissure caries in immature molars with covering opercula. BACKGROUND DATA: In pediatric dentistry, it is not unusual to find partially erupted immature permanent teeth, especially with opercula. Conventional dental caries prevention is not effective in these cases because of the immaturity of tooth substance and the presence of the opercula, which accumulate a substantial amount of plaque. MATERIALS AND METHODS: The CO2 laser was used on 22 immature erupting molars with opercula. In each case, we first cut the operculum with a CO2 laser in a 2- or 3-watt continuous mode. Then, the occlusal surface was irradiated spot by spot along the pits and fissures of the molar using a CO2 laser in a 2-watt pulsed mode with 0.2 sec of irradiation time (average power, 0.3 watt; pulse width, 10 msec; repetition time, 15 Hz; energy density, 15 J/cm2). Each of the studied teeth was clinically examined for dental caries for 3 years. RESULTS: It took less than 2 min to cut the operculum, and there was no bleeding. The irradiation imparted acid resistance to the teeth without any discomfort to the patients. The patients did not complain of any pain after the procedure. Only two of the studied teeth developed dental caries during the observation period. CONCLUSION: We conclude that a CO2 laser might be an effective mode of treatment in the prevention of pit and fissure caries in partially erupted permanent molars covered with opercula.

Carbon Dioxide↗
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↗