PubMed Health⌕ Search

Biomedical subjects

N Yanai

Publications and source records attributed to N Yanai.

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

[Effectiveness of docetaxel plus cisplatin in large cell lung cancer showing little response to prior chemotherapy with MVP].

The present patient was a 53-year-old male who had large cell lung cancer of c-T4N1M0. We administered multi-drug regimen including mitomycin C, vindesine and cisplatin (CDDP) because of cancer invasion into the great vessels seen on a chest CT. After 3 courses, the cancer showed no change in size. Therefore, we adopted chemotherapy of docetaxel (Taxotere: TXT) and CDDP. After 4 courses, the size of the mass had decreased (partial response). The only major toxic defect was grade 3 neutropenia. A good response to TXT and CDDP could lead to complete resection of lung cancer. It is suggested that TXT is effective in the treatment of large cell lung cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Alteration of the increase in intracellular [Ca(2+)] in proliferating smooth muscle cells.

Proliferation of smooth muscle cells (SMC) has a role in the development of cardiovascular diseases. We investigated the alteration of contractile signals in proliferating SMC by measuring the increase in intracellular [Ca(2+)] to endothelin-1 (ET-1), noradrenaline (NA), or angiotensin II (AgII). We found that the increase in intracellular [Ca(2+)] by NA or ET-1 decreased in proliferating SMC in comparison to growth-arrested SMC. The increase in intracellular [Ca(2+)] by AgII was stable between the cells. Immunoblotting of inositol 1,4,5-trisphosphate receptors (IP(3)Rs) which are responsible for the mobilization of Ca(2+) by those vasoactive substances revealed that expression of IP(3)R type 1 and type 2 was decreased. Expression of IP(3)R type 3 was increased. The altered Ca(2+) signaling by the cell growth might involve the expression of IP(3)R subtypes.

Animals↗
PubMed1999

A novel stromal cell-dependent hematopoietic cell line established from temperature-sensitive SV40 T-antigen transgenic mice.

A novel primitive hematopoietic cell line, THS119, was established from lineage marker negative (Lin-)/Sca-1+ cells from bone marrow of temperature-sensitive (ts) SV40 T-antigen transgenic mice after lengthy passaging by coculture with TBR59 bone marrow stromal cells. THS119 cells exhibited immature primitive hematopoietic cells such as forming cobblestones underneath the stromal cell layers. They retained properties of hematopoietic stem cells as shown by expression of c-Kit, Sca-1 and CD34low, but lacked hematopoietic lineage surface markers of differentiated hematopoietic cells (Gr-1, TER119, Mac-1, CD3, B220). RT-PCR analysis showed that THS119 cells exhibited multiple expression of both earlier developmental markers of myeloid, lymphoid and the hematopoietic cell specific transcription factors. THS119 cells showed temperature-dependent growth reflecting ts T-antigen, and their maintenance was TBR59 stromal cell-dependent. The requirement of stromal cells could not be replaced by cytokines, however, an IL-3 or IL-7 dependent cell line was generated after prolonged culture of THS119 cells on the stromal cells in the presence of these cytokines, and these cytokine-dependent cell lines exhibited phenotypes similar to the parental cells in their gene expression. SCF/c-Kit interaction is one factor required for their maintenance, but involvement of other factor(s) in the conditioned medium of TBR59 stromal cells was suggested. A novel immature hematopoietic cell line, THS119, may provide an appropriate experimental system to resolve how hematopoietic cells are kept in a primitive phase within a hematopoietic microenvironment.

Animals↗
PubMed1999

Vaginal outflow tract obstruction by graft-versus-host reaction.

We describe a 25-year-old patient suffering from vaginal outflow obstruction which presented as secondary amenorrhea during hormone replacement therapy. The patient had undergone bone marrow transplantation for acute myelocytic leukemia, which caused ovarian failure. Oral mucositis associated with a chronic GVH reaction also occurred. For 3 years she was treated with HRT and had regular menses which gradually ceased and were associated with dyspareunia and abdominal cramps. Abdominal US examination demonstrated hematocolpus. Sonography guided adhesiolysis of a dense vaginal obstruction allowed free drainage with histologic confirmation of a graft-versus-host reaction. The possibility of vaginal stricture or obstruction should be considered in all patients after BMT who suffer from graft-versus-host disease.

Adult↗
PubMed1999

A novel stromal cell-dependent B lymphoid stem-like cell line that induces immunoglobulin gene rearrangement.

A stroma-dependent B lymphoid cell line (B31-1) has been established by coculturing sorted stem cells on a novel bone marrow stromal cell line (TBR31-1). B31-1 cells express B220, but do not express other B lymphoid differentiation markers including CD43, heat stable antigen (HSA), or surface immunoglobulin (Ig) M (sIgM), and their Ig heavy chain (IgH) gene loci are germ-line in configuration. The addition of interleukin (IL)-7 or coculture with another stromal cell line, ST2, induces D-J rearrangement of the IgH gene and B lymphocyte differentiation markers. B31-1 cells restore an in vivo repopulation activity to lethally irradiated mice, and the repopulated cells differentiate to HSA+ pre-B cells.Continuous coculture results in two distinct populations, B220(-) c-Kit+ cells and B220(+) c-Kit+ cells; B220(-) c-Kit+ cells are self-renewed and differentiate to B220(+) c-Kit+ cells, while B220(+) c-Kit+ cells produce only B220(+) c-Kit+ cells. Both B220(-) and B220(+) cells similarly express the IgH germ-line transcript (Imu), mRNAs for recombinase (TdT, Rag-1, and Rag-2), and lymphoid-specific transcription factors (Pax-5, EBF, E12/E47, Oct-2, and Ikaros), but the DNA binding activity of Pax-5, EBF, Oct-2, and E2A are low in B220(-) cells and while high in B220(+) cells. These results suggest the existence of at least two active states in the IgH locus before the induction of IgH gene rearrangement during B lymphopoietic development.

Animals↗
PubMed1999

Establishment of SV40-tsA58 transgenic rats as a source of conditionally immortalized cell lines.

To isolate a variety of rat cell lines with differentiated functions, we established transgenic rat lines expressing the temperature-sensitive large T-antigen of simian virus 40 (SV40) tsA58 mutant under the control of the SV40 large T-antigen itself. We microinjected the DNA into 564 eggs of Wistar rat and 23 independent transgenic candidates were obtained. Ten pups died before weaning and eight transgenic rats could not transmit the transgene to the progeny. Finally, five lines of the transgenic rat were established. Although one line (#1511-6) had low reproductivity, the other four lines reproduced normally. Three out of the four lines (#1507-2, #1509-7, #1519-8) appeared normal but the other line had tumors in the brain and subcutaneous tissue at 3 weeks of age (#1511-6), and in the kidneys and subcutaneous tissue at 18 to 19-weeks of age (#1507-5). Fibroblast cells prepared from transgenic fetuses of lines #1507-5 and #1519-8 expressed the transgene and exhibited temperature-dependent growth. Both of the lines (#1507-5 and #1519-8) were successfully generated to be homozygous by sibling mating of transgenic offspring. These transgenic rat lines have bred through many generations and have been established to be a ready source of novel conditionally immortalized cell lines.

Animals↗
PubMed1999

[Preoperative evaluation of cardiac disease for patients with lung cancer: usefulness of treadmill exercise electrocardiogram].

118 patients with lung cancer who underwent treadmill exercise electrography (ECG) as part of their preoperative evaluation, were investigated for postoperative events. On the treadmill exercise ECG 27 patients were positive and 91 were negative. The more elderly patients tended to reveal ischemic findings in treadmill exercise ECG. Of the 71 patients with normal of result by ECG at rest, 15 patients (21.1%) had postoperative ischemic change on ECG. As a result, it was considered that this examination was insufficient to detect latent ischemic heart disease. The patients who had a discontinued at stage 2 or less of the Bruce protocol and had a negative result by treadmill exercise ECG, were classified as insufficient group and separated from the others. (27/118 patients). This group consisted of advanced age (p < 0.05) who tended to experience postoperative events. In the sufficient group, patients showed ischemic events predominantly on ECG at postoperative period (p < 0.01). We concluded that as preoperative screening of heart disease prior to lung cancer surgery ECG at rest was not adequate while treadmill exercise ECG was useful.

Adult↗
PubMed1998

AML1(-/-) embryos do not express certain hematopoiesis-related gene transcripts including those of the PU.1 gene.

The AML1 and PEBP2beta/CBFbeta genes encode the DNA-binding and non-binding subunits, respectively, of the heterodimeric transcription factor, PEBP2/CBF. Targeting each gene results in an almost identical phenotype, namely the complete lack of definitive hematopoiesis in the fetal liver on embryonic day 11.5 (E11.5). We examined and compared the expression levels of various hematopoiesis-related genes in wild type embryos and in embryos mutated for AML1 or PEBP2beta/CBFbeta. The RNAs were prepared from the yolk sacs of E9.5 embryos, from the aorta-gonad- mesonephros regions of E11.5 embryos and from the livers of E11.5 embryos and RT-PCR was performed to detect various gene transcripts. Transcripts were detected for most of the hematopoiesis-related genes that encode transcription factors, cytokines and cytokine receptors, even in tissues from homozygously targeted embryos. On the other hand, PU.1 transcripts were never detected in any tissue of AML1(-/-) or PEBP2beta/CBFbeta(-/-) embryos. In addition, transcripts for the Vav, flk-2/flt-3, M-CSF receptor, G-CSF receptor and c-Myb genes were not detected in certain tissues of the (-/-) embryos. The results suggest that the expression of a particular set of hematopoiesis-related genes is closely correlated with the PEBP2/CBF function.

Animals↗
PubMed1998

Identification of Bach2 as a B-cell-specific partner for small maf proteins that negatively regulate the immunoglobulin heavy chain gene 3' enhancer.

Maf family transcription factors are important regulators in various differentiation systems. Putative Maf recognition elements (MAREs) are found in the 3' enhancer region of the immunoglobulin heavy chain (IgH) gene. These elements are bound in B-cell extracts by a heterodimeric protein complex containing both Bach2 and a small Maf protein. Analysis of normal hematopoietic cells revealed that Bach2 is specifically expressed in B cells. Bach2 is abundantly expressed in the early stages of B-cell differentiation and turned off in terminally differentiated cells. Bach2 acts together with MafK as a negative effector of the IgH 3' enhancer and binds to the co-repressor SMRT (silencing mediator of retinoid and thyroid receptor). Hence the Bach2-small-Maf heterodimer may represent the first example of a B-cell lineage, and of a developmental stage-restricted negative effector of the MARE in the IgH 3' enhancer region.

B-Lymphocytes↗
PubMed1998

Involvement of NK1+ T cells and their IFN-gamma production in the generalized Shwartzman reaction.

IL-12 (or LPS) priming and subsequent challenge by LPS produces the generalized Shwartzman reaction. IFN-gamma induced by IL-12 is a crucial cytokine in the priming phase. In vivo depletion of both NK cells and NK1+ alphabeta T cells of mice by anti-NK1.1 Ab greatly reduced the elevation of serum IFN-gamma induced by IL-12 and significantly reduced mortality after subsequent injection of LPS, whereas depletion of NK cells alone by anti-asialo GM1 Ab only partially decreased serum IFN-gamma, and lethality was not changed. Cell sorting and culture experiments confirmed that liver NK1+ alphabeta T cells of IL-12-injected mice produced greater amounts of IFN-gamma than did liver NK cells. MHC class I-deficient mice of C57BL/6 background, which lack a majority of NK1+ alphabeta T cells, produced low amounts of IFN-gamma by IL-12; no mortality was observed after the LPS challenge. However, production of TNF-alpha in the second phase (after LPS challenge) was not inhibited by depletion of NK cells alone or both subsets. IL-12 and subsequent LPS challenge activated NK1+ alphabeta T cells in the liver and induced strong cytotoxicity of these cells not only against tumor cells (including Fas-negative tumors) but also against a syngeneic hepatocyte cell line. Our findings show that IFN-gamma produced by NK1+ alphabeta T cells is essential for the IL-12 priming of the Shwartzman reaction, and the autoreactivity of NK1+ alphabeta T cells in the liver is involved in the hepatic disorders that are sometimes caused by IL-12, LPS, or the generalized Shwartzman reaction.

Adjuvants, Immunologic↗
PubMed1998

Integrin-associated protein (IAP, also termed CD47) is involved in stroma-supported erythropoiesis.

Erythropoiesis is regulated by the hematopoietic microenvironment of the spleen, fetal liver, and bone marrow in mice. We previously showed that established stromal cells from these organs selectively support erythropoiesis in vitro. To identify the cell surface molecule(s) on the stromal cells involved in erythropoiesis, we raised monoclonal antibodies (MAbs) to MSS62 stromal cells derived from newborn spleen and obtained MAb100.1, which partially inhibited the stroma-supported erythropoiesis in vitro. Using an expression cDNA library of MSS62 cells, we cloned a gene encoding the protein recognized by MAb100.1 and identified it as integrin-associated protein (IAP, also termed CD47), which may play a general role in integrin-mediated signal transduction. IAP/CD47 is expressed in the stromal cells of spleen, fetal liver, and bone marrow, and in a variety of hematopoietic cells including erythroblasts. Thus, IAP may be partly involved in the erythropoietic supporting ability of the stromal cells.

Amino Acid Sequence↗
PubMed1998

Involvement of stromal membrane-associated protein (SMAP-1) in erythropoietic microenvironment.

Erythropoiesis is regulated by the hematopoietic microenvironment of the spleen and fetal liver in mice. We showed that established stromal cells of these organs selectively support erythropoiesis in vitro. To identify the cell surface molecule(s) on the stromal cells involved in erythropoiesis, we raised monoclonal antibodies against the stromal cells. Using one of these antibodies (11D), we cloned a new gene named smap-1 (stroma membrane-associated protein-1). The SMAP-1 protein deduced from the nucleotide sequence of the cDNA was a newly identified membrane protein with direct repeats of the KKD/E units found in MAP1A and MAP1B, which is involved in the association with microtubules. By transfection of the anti-sense smap-1 cDNA into the stromal cells, we showed that SMAP-1 may have a stimulatory effect on stroma-supported erythropoiesis. Its expression was detected in the yolk sac, fetal liver, spleen, and bone marrow, and was correlated with their erythropoietic activity.

Amino Acid Sequence↗
PubMed1998

Identification and expression of the Bacillus subtilis fructose-1, 6-bisphosphatase gene (fbp).

The Bacillus subtilis fbp gene encoding fructose-1,6-bisphosphatase (FBPase) was originally identified as yydE. The fbp gene was expressed at a fairly constant level in cells undergoing glycolysis or gluconeogenesis. fbp transcription was initiated 94 bp upstream of the translation initiation codon, resulting in a 2.4-kb monocistronic transcript. Interestingly, B. subtilis FBPase exhibited no significant similarity to other FBPases in protein sequence databases.

Bacillus subtilis↗
PubMed1998

Regulation of myeloid and lymphoid development of hematopoietic stem cells by bone marrow stromal cells.

Development of hematopoietic stem cells is regulated by stromal cells of the bone marrow. Many stromal cell lines have been established from temperature-sensitive SV40 large T-antigen gene transgenic mice and used to examine regulation of the purified stem cells. When the sorted stem cells were cocultured on the stromal cell layers, cobblestone formation was induced by the stromal cells. The cobblestones were formed by finite cell division (8 divisions on average) of sorted Lin- c-Kit+ Sca1+ stem cells committed to myeloid or lymphoid lineages. These stromal cell lines showed variable activities supporting the stem cell development. In one stromal cell line, TBR59, two waves of cobblestone formation committed to either myeloid lineage or lymphoid lineage were induced. TBR31-1, another bone marrow stromal cell line, induced only the cobblestone formation committed to lymphoid lineage. These results indicate that the bone marrow stromal cells selectively induce lineage-specific commitment of the stem cells. Both cobblestone formations require c-Kit function as well as adhesive interaction through VLA4 and VCAM1.

Animals↗
PubMed1998

Selective proliferation of lymphoid cells from lineage-c-Kit+ Sca-1+ cells by a clonal bone marrow stromal cell line.

To understand the regulatory mechanisms involved in the development of hematopoietic stem cells, we cultured lineage-negative, c-Kit+ Sca-1+ stem cells sorted from bone marrow cells by a fluorescence-activated cell sorter (FACS) on layers of bone marrow stromal cell lines established from SV40 T-antigen gene transgenic mice. We previously reported that the TBR59 stromal cell line induced two sequential cobblestone formations: the first formation committed to the myeloid and the second to the lymphoid lineage. After examination of many other bone marrow stromal cell lines, we found that TBR31-1 stromal cells supported only lymphoid development of the sorted stem cells. The sorted stem cells proliferated by forming cobblestones and the cells were released from the cobblestones. Most released cell populations were B220-positive lymphoid cells; cell production continued for 2 months. Addition of G-CSF or M-CSF produced only a slight effect on myeloid development. FACS analysis of the released cells showed that the B-lymphoid-committed progenitors developed into mature B-cells by expressing surface immunoglobulin M. These results indicate that TBR31-1 bone marrow stromal cells selectively support B-lymphoid development, whereas TBR59 cells support both myeloid and lymphoid development of stem cells.

Animals↗
PubMed1998

[Pulmonary tuberculosis in the elderly].

Clinical problems of pulmonary tuberculosis in the elderly patients were discussed. As for diagnosing tests, chest X ray sometimes shows atypical findings in patients with pre-existing pulmonary diseases (i.e. pulmonary emphysema, interstitial pneumonia and etc). It is most important to get bacteriologic evidence from suspected patients of pulmonary tuberculosis. Elderly patients have co-existing diseases except pulmonary tuberculosis. Controlling co-existing diseases is essential for treatment of pulmonary tuberculosis in the elderly patients. Treatment with standard chemotherapy leads to good result even in the elderly. However, we have to investigate the mechanism of rush cases, who dies in a few months in spite of adequate chemotherapy.

Aged↗