Search PubMed⌕ Search

Biomedical subjects

N Komatsu

Publications and source records attributed to N Komatsu.

At least 37 records · Page 2Linked to original sources
PubMed2000

Familial frontotemporal dementia with a P301L tau mutation in Japan.

We have reported the family line with frontotemporal dementia (FTD) in Japan. This family line has so far included four patients. Patient II-1 (man) had a 10 year history of slowly progressive personality and behavioral changes and died at the age of 56. His neuropathological examination showed severe atrophy of the bilateral frontal and temporal cortices with neuronal loss, gliosis and superficial spongiosis. Pick bodies were not found. The neuropathological diagnosis was atypical Pick's disease without Pick bodies or Pick-type in FTD. Patient III-2 is patient II-1's oldest daughter and was taken ill with personality change at the age of 52. She died at the age of 68. Patient III-4 is patient II-1's second daughter. Her onset with strange speech and behavior was at the age of 59. Patient III-5 is patient II-1's oldest son. He also had onset with personality change at the age of 54 and had the P301L mutation in tau. In all III generation cases CT/MRI revealed circumscribed frontotemporal atrophy. Patient III-5's PET/SPECT showed signs of hypoperfusion or hypometabolism in the bilateral frontotemporal areas. This is the first report of familial FTD with the P301L mutation in Japan.

DNA Mutational Analysis↗
PubMed2000

Mutations of the E2F4 gene in hematological malignancies having microsatellite instability.

Mutations of coding repeats within the E2F4, TGF-betaRII, BAX, IGFIIR, and hMSH3 are critical targets of microsatellite instability (MSI) in many kinds of cancers. We analyzed 9 childhood acute lymphoblastic leukemia (ALL) samples, 5 acute myelocytic leukemia (AML) samples, and 10 adult T-cell leukemia (ATL) samples having MSI to determine whether they had mutations of the E2F4, TGF-betaRII, BAX, IGFIIR, and hMSH3 genes. Frameshift mutations were found at trinucleotide repeats within a coding exon of the E2F4 gene in 2 of 10 (20%) ATL samples and 1 of 9 (11%) childhood ALL samples. No mutations were found in the TGF-betaRII, BAX, IGFIIR, and hMSH3 genes. E2F4 is a transcription factor that influences the cell-cycle progression. These results suggest that mutations of the E2F4 gene, presumably caused by an abnormality of one of the DNA repair genes, may play an important role in development of ATL and childhood ALL. (Blood. 2000;95:1509-1510)

Adult↗
PubMed2000

Constitutional t(3;11)(p21;q23) in a family, including one member with lymphoma: establishment of novel cell lines with this translocation.

We describe a family with an inherited constitutional chromosome translocation (3;11) (p21;q23). Of three proven translocation carriers, one had duodenal malignant lymphoma (B-cell diffuse lymphoma, medium-sized cell type). The t(3;11)(p21;q23) was detected not only in hematopoietic cells including the patient's lymphoma cells, non-pathological bone marrow, and phytohemagglutinin-stimulated peripheral blood, but also in fibroblasts of the skin. We have successfully established an Epstein-Barr virus-transformed B-cell line and a Herpesvirus saimiri-transformed T-cell line from the patient, and found that both cell lines also carried this translocation. The patient's asymptomatic mother and sister had the same chromosomal abnormality. Chromosomal abnormalities of the 11q23 band occur frequently in various hematopoietic malignant disorders, and 3q21 has been linked to the pathogenesis of several solid tumors including carcinomas of the kidney, lung, and breast. Although 11q23 is known to recombine with many different chromosomal segments, t(3;11)(p21;q23) has not been reported to our knowledge. Further assessment is warranted to clarify if this constitutional translocation predisposes to certain malignancies. Our cell lines carrying the novel chromosome translocation would be useful for the molecular analysis of the rearranged genes involving both 3p21 and 11q23.

Adult↗
PubMed2000

Functional characterization of the two alternative promoters of human p45 NF-E2 gene.

OBJECTIVE: The transcription factor NF-E2, a heterodimeric protein complex composed of p45 and small Maf family proteins, is considered crucial for the proper differentiation of erythrocytes and megakaryocytes in vivo. We report the results of studies aimed at understanding the regulatory mechanisms controlling p45 gene expression in erythroid cells. MATERIALS AND METHODS: Human p45 mRNAs have two alternative isoforms, aNF-E2 and fNF-E2, and these isoforms are transcribed from the alternative promoters. We investigated lineage-specific expression of both isomers in human erythroid and megakaryocytic cells by reverse transcriptase polymerase chain reaction or Northern blot analysis. For functional characterization of both promoters, plasmids in which reporter genes were placed under the control of a series of truncated or mutated promoter fragments were transfected to human hematopoietic cell lines. RESULTS: When CD34(+) cells isolated from human cord blood were induced to unilineage erythroid or megakaryocytic differentiation in liquid suspension culture, both transcripts, although barely detected at day 0, were induced in both erythroid and megakaryocytic cultures. fNF-E2 mRNA was found to be more abundant in erythroid cells than megakaryocytic cells at day 7 of culture. Although both isomers were expressed in human erythroid-megakaryocytic cell lines, megakaryocytic maturation with loss of erythroid phenotype induced by phorbol 12-myristate 13-acetate (PMA) resulted in exclusive downregulation of fNF-E2, suggesting that fNF-E2 promoter is more erythroid specific. Functional analysis of fNF-E2 promoter showed that the promoter is active only in erythroid-megakaryocytic cells and that the double GATA site in the proximal region is necessary for its efficient activity. CONCLUSION: These results suggest that GATA proteins, which govern the differentiation of erythroid lineage cells, are required for full promoter activity of the p45 gene.

Binding Sites↗
PubMed2000

Construction of ELISA system to quantify human ST2 protein in sera of patients.

The human ST2 gene can be specifically induced by growth stimulation in fibroblastic cells, and can also be induced by antigen stimulation in Th2 cells. The gene encodes a soluble secreted protein, ST2, and a transmembrane protein, ST2L, which are closely related to the interleukin-1 receptor. To gain insight into the biological roles of the ST2 gene, three monoclonal antibodies (MAbs) against human ST2 gene products were obtained. To obtain these antibodies, immunization was carried out using two different immunogens: purified soluble human ST2 protein (hST2), and COS7 cells, which express the extracellular portion of human ST2L. 2A5 and FB9 MAbs were derived from the immunization with soluble hST2, and HB12 was derived from the COS7 cell immunization. All three antibodies were shown to detect native forms of the human ST2 gene products by immunoprecipitation, flow cytometry, and enzyme-linked immunosorbent assay (ELISA). In the competitive ELISA using biotinylated and nonlabelled MAbs, neither FB9 nor HB12 affected the binding of 2A5 to ST2 gene products. Based on this result, we constructed a sandwich ELISA system using 2A5 and FB9 to measure the concentration of soluble hST2 in sera. The ELISA, combined with the flow cytometry using these antibodies, will be a useful tool for elucidating the functions of human ST2 gene products in individuals.

Animals↗
PubMed2000

A case of bilateral heel ulcers associated with hydroxyurea therapy for chronic myelogenous leukemia.

Bilateral heel skin ulcers developed in a 50-year-old male in the chronic phase of chronic myelogenous leukemia who had been receiving hydroxyurea (HU) therapy for 3 years. Histological examination showed perivascular lymphocytic inflammation without vasculitis. After interruption of HU administration, the heel ulcers were completely resolved within 2 months. The clinical course strongly suggested that the heel ulcers were induced by long-term HU therapy.

Antineoplastic Agents↗
PubMed2000

Depletion of intracellular NAD(+) and ATP levels during ricin-induced apoptosis through the specific ribosomal inactivation results in the cytolysis of U937 cells.

Our previous studies demonstrated that ricin induces the apoptotic death of U937 cells as evidenced by DNA fragmentation, nuclear morphological changes, and increases in caspase-like activities. In this study, we have found that intracellular NAD(+) and ATP levels decrease in ricin-treated U937 cells and that this decrease is followed by the ricin-mediated protein synthesis inhibition. The PARP inhibitor, 3-aminobenzamide (3-ABA), prevents the depletion in NAD(+) and ATP levels and concomitantly protects U937 cells from the lysis that follows ricin treatment. Hence, the protective action of 3-ABA is due to the inhibition of PARP and does not result from its other pharmacological side effects. Moreover, the enzymatic activity of PARP gradually increases and reaches a maximum level after ricin exposure for 3 h, whereas no significant change in activity was observed in untreated cells. However, 3-ABA has no effect on ricin-mediated DNA fragmentation. In addition, immunoblot analysis revealed that significant PARP cleavage occurred more than 12 h after ricin addition, while DNA fragmentation reached a maximum level within 6 h of incubation. Thus, in the case of ricin-induced apoptosis, it appears that PARP cleavage is not an early apoptotic event associated with the onset of apoptosis. Our results suggest that multiple apoptotic signaling pathways may be triggered by ricin-treatment. Probably, the pathway leading to cell lysis via PARP activation and NAD(+) depletion is independent of the pathway leading to DNA fragmentation in which caspases may be profoundly involved. Other protein synthesis inhibitors, including diphtheria toxin and cycloheximide, were less effective in terms of inducing DNA fragmentation and cytolysis, even at concentrations that cause significant inhibition of protein synthesis. Thus, a specific ricin action mechanism through which ribosomes are inactivated may be responsible for the apoptotic events induced by ricin.

Adenosine Triphosphate↗
PubMed2000

Identification of epidermal growth factor mRNA-expressing cells in the mouse anterior pituitary.

Epidermal growth factor (EGF) produced within the pituitary gland is associated with the growth of pituitary cells in rats. The aim of the present study was to localize EGF- and EGF receptor-expressing cells, and to clarify the involvement of EGF in DNA replication in 2-month-old male mouse pituitary cells. In situ hybridization of the pituitaries of these mice demonstrated that EGF mRNA was expressed in the anterior and intermediate lobes. Within the anterior pituitary, EGF mRNA-expressing cells were medium-sized and round, and made up 40% of the total number of secretory cells. EGF receptor mRNA was only detected in anterior pituitary cells. Forty-seven percent anterior pituitary cells expressed EGF receptor mRNA. An immunocytochemical study showed that most somatotropes and some mammotropes expressed EGF mRNA. When anterior pituitary cells were enzymatically dissociated and cultured in serum-free medium, RT-PCR demonstrated both EGF mRNA and EGF receptor mRNA expression. Treatment with EGF (1 and 10 ng/ml) for 5 days stimulated DNA replication in mammotropes and corticotropes. These results indicate that the DNA replication in mammotropes and corticotropes is regulated by the paracrine and/or autocrine activity of EGF produced at least in part by these cell types themselves.

Animals↗
PubMed2000

Relationship between MRI findings and prognosis for patients with general paresis.

MRI was performed in 7 patients with general paresis before or at a very early stage of treatment. A large dose of antibiotics, mainly penicillin, was given to all patients, and the effects of treatment, the patients' outcome, and MRI findings were investigated. Three of the 7 patients had MRI findings of atrophy of the medial temporal lobe including the hippocampus. In the medial temporal lobe atrophy group, a personality change or general dementia remained even after the treatment was completed, and outcome in social functioning was poor. Medial temporal lobe atrophy may be a poor prognostic sign in general paresis.

Adult↗
PubMed2000

Isolated ricin B-chain-mediated apoptosis in U937 cells.

We have previously reported that ricin, a toxic lectin that inhibits protein synthesis induced apoptotic cell death. In this study, we have found that isolated ricin CM-B-chain, which has no effect on cellular protein synthesis, induced DNA fragmentation in U937 cells in a dose- and time-dependent manner, albeit it required a longer incubation time and higher concentration than those of holotoxin ricin. Z-Asp-CH2-DCB, a caspase family inhibitor and serine protease inhibitor, 3,4-dichloroisocoumarine (DCI) effectively inhibited the CM-B-chain-mediated DNA fragmentation as well as in ricin. Thus, like ricin, multiple proteases with different substrate specificity may also be involved in the CM-B-chain-mediated apoptotic pathway. Furthermore, BFA inhibited both ricin- and CM-B-chain-mediated DNA fragmentation, suggesting an intracellular vesicle transport system through the Golgi complex may be involved in the apoptotic induction by these proteins as a common feature. On the other hand, cycloheximide (CHA) strongly increased the CM-B-chain-mediated DNA fragmentation, but inhibited ricin-mediated DNA fragmentation. The opposite effects of CHA may reflect the difference in the apoptotic mechanism between ricin and CM-B-chain. In conclusion, our results suggest that ricin-B-chain can induce apoptosis through its lectin activity, but the underlying mechanism may be distinct from that of ricin in which the A-chain contributes profoundly to the apoptotic induction.

Apoptosis↗
PubMed2000

Effects of glutathione-related compounds on increased caspase-3 and caspase-6-like activities in ricin-treated U937 cells.

Both caspase-3 and -6-like activities increased in the cytosolic extract from ricin-treated U937 cells that were inhibited by glutathione disulfide (GSSG) in a dose-dependent manner, but reduced glutathione (GSH) had no effect. Interestingly, caspase-6 like activity was more sensitive to GSSG than caspase-3 like activity. The IC50 of GSSG against caspase-3 and caspase-6 like activities were estimated to be 2.8 mM and 0.8 mM, respectively. Cystine but not cysteine also showed similar inhibitory effect on caspase-3-like activity. The inhibitory effect of GSSG on these caspase-like activities was prevented by the addition of DTT to the assay mixture. These results suggest that an intact disulfide portion of GSSG is required for the effective inhibition of caspase activity.

Apoptosis↗
PubMed2000

In vitro detection of equine arteritis virus from seminal plasma for identification of carrier stallions.

Equine arteritis virus (EAV) was readily isolated in RK-13 cell monolayers by plaque assay from seminal plasma of experimental carrier stallions when they contained high titers of virus regardless of the presence of non-viral cytotoxicity in the seminal plasma. The cytotoxicity interfered with virus isolation from seminal plasma which contained virus at titers less than 10 PFU/ml. However, it was possible to detect the virus in seminal plasma pretreated with PEG (#6000). EAV was consistently identified by RT-PCR from crude seminal plasma which contained virus at titers of more than 10(2.7) PFU/ml. In vitro detection of EAV by virus isolation supplemented with RT-PCR using seminal plasma was proved to be an effective alternative to the standard test mating as a diagnostic method for carrier stallions.

Animals↗
PubMed2000

Type 1 diabetes mellitus caused by treatment with interferon-beta.

A 57-year-old man was referred to our outpatient clinic after interferon-beta (IFN-beta) treatment for 7 weeks. While IFN-beta therapy was continued in our outpatient clinic, his blood glucose level increased gradually, and he was admitted to our hospital for hyperglycemia. The patient was prescribed a 1,600-kcal diet and intensive insulin therapy was performed. GAD antibody became positive 15 months after the start of IFN therapy, and disappeared 27 months after the start of IFN therapy. Insulin secretion was depleted and the patient had HLA-DR4, B54, and DRB1*0405. This appears to be a case of type 1 diabetes mellitus induced by administration of IFN-beta alone.

Antiviral Agents↗
PubMed2000

Autologous peripheral blood stem cell transplantation for adults with B-lineage acute lymphoblastic leukemia: a pilot study.

We conducted a pilot study on autologous peripheral blood stem cell transplantation (PBSCT) for 11 adults with B-lineage acute lymphoblastic leukemia (ALL) in first complete remission (CR) or even in those with more advanced stages. All patients achieved CR by induction therapy, of whom 10 were treated with anthracycline, vincristine and prednisolone-based regimens. After consolidation therapy, all patients except one received high-dose cytarabine followed by granulocyte colony-stimulating factor (G-CSF) administration to collect PBSCs. Ten patients received busulfan 4 mg/kg for 4 days, etoposide 20 mg/kg for 3 days and ranimustine 200 mg/m2 for 2 days as a conditioning regimen. One received a regimen consisting of etoposide, cyclophosphamide and total body irradiation. From day 1, G-CSF was given intravenously, and no additional chemotherapy was administered. At the median follow-up time of 30.8 months, four of six patients with standard-risk B-lineage ALL survived within the range of 19.7 to 85.4 months without relapse. In contrast, only one of five with high-risk B-lineage ALL survived for 36.3 months without relapse. Autologous PBSCT as post-remission therapy may prolong CR in adults with standard-risk B-lineage ALL.

Adolescent↗
PubMed2000

[Low-dose prednisolone therapy for idiopathic thrombocytopenic purpura].

Prednisolone (PSL) is widely used for the treatment of idiopathic thrombocytopenic purpura (ITP). We compared the effects of a relatively low dose (0.5 mg/kg/day, LD group) of PSL and the conventional dose (1.0 mg/kg/day, CD group) on 59 ITP patients. Twenty-six patients were treated with low-dose PSL, and 23 patients with the conventional dose. No statistically significant difference was observed in the complete remission rates for the LD group (35%) and the CD group (39%). However, the mean duration of hospitalization was significantly (p < 0.001) shorter for LD group patients than for patients in the CD group (20 days versus 50 days, respectively). In conclusion, low-dose PSL may be as effective as the conventional dose and capable of reducing the cost of hospitalization, thus, improving the quality of life for patients with ITP.

Anti-Inflammatory Agents↗
PubMed2000

[Two cases of acute myelogenous leukemia complicated with fatal gastrointestinal tract bleeding after treatment with idarubicin and cytarabine].

We describe herein two newly diagnosed patients with acute myelogenous leukemia (AML), who were treated twice with an idarubicin hydrochloride (IDR)-containing regimen as a response-orientated induction therapy. Both patients had severe gastrointestinal tract hemorrhage complications at their nadir. The two patients were as follows: a 35-year-old male, FAB-M4, and a 47-year-old female, FAB-M0. They received the same induction chemotherapy (IDR 12 mg/m2 for four days and cytarabine 100 mg/m2 for ten days). No response (NR) was obtained in either, so they underwent the same regimen again. During the period of myelosuppression, they developed severe gastrointestinal hemorrhage. One died of sepsis, and the other of acute respiratory distress syndrome without a recovery in bone marrow. The fetal gastrointestinal tract complications may have been due to severe myelosuppression and mucosal damage in these patients. Careful observation will be needed to prevent such severe complications after the treatment with IDR.

Adult↗
PubMed2000

All-trans-retinoic acid treatment for chemotherapy-resistant acute adult T-cell leukemia.

We report a case in which treatment with all-trans-retinoic acid (ATRA) improved the clinical features of a 47-year-old female patient with acute adult T-cell leukemia (ATL). The patient was first treated several times with combination chemotherapy. but the number of ATL cells increased and other clinical manifestations progressed. ATRA 60 mg was then administered daily. ATRA treatment dramatically improved the patient's clinical features. In vitro examination revealed that ATRA inhibited the growth of ATL cells from the patient. These findings suggest that ATRA may be a useful treatment for patients with chemotherapy-resistant acute ATL.

Acute Disease↗