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Biomedical subjects

Y Deguchi

Publications and source records attributed to Y Deguchi.

At least 73 records · Page 4Linked to original sources
PubMed1993

High level expression of the homeobox gene HB24 in a human T-cell line confers the ability to form tumors in nude mice.

The human homeobox gene HB24 is constitutively expressed in bone marrow progenitor cells and is inducible in lymphocytes. Transfection of HB24 into the T-cell line Jurkat under the control of the beta-actin promoter resulted in enhanced cell growth and induction of several growth-related genes. In this study we have examined whether the presence of high levels of HB24 alters the tumorigenicity of Jurkat cells in nude mice. Subcutaneous injection of 1-2 x 10(6) Jurkat cells or Jurkat cells transfected with a control expression vector into nude mice failed to produce tumors. However, injection of a similar number of HB24-transfected Jurkat cells resulted in local tumor formation within 4 weeks and grossly apparent metastatic lesions within 8 weeks. Histopathological analysis of tissues from the local and metastatic lesions demonstrated predominantly lymphoid cells, consistent with the morphological appearance of the injected cell line. Freshly isolated tumor cells from the nude mice incorporated similar levels of [3H]thymidine as the HB24-transfected Jurkat cells and 2-fold more than the parent Jurkat cells. Northern blot analysis of RNA prepared from the tumors revealed expression of human interleukin 2, interleukin 2 receptor alpha-chain, HB24, and CD4. Flow cytometric analysis of the tumor cells revealed human CD4 expression but not murine CD4, confirming the human origin of the tumor cells. Media conditioned by the tumor cells contained large amounts of interleukin 2. Since natural killer cell activity is the primary immunological response against tumors in nude mice, the effects of HB24 on the responsiveness to natural killer cell-mediated cell lysis was examined. No differences in natural killer cell killing of the parent Jurkat cells and the HB24-transfected cells were observed. These data, in conjunction with recent data implicating other homeobox-containing genes in the pathogenesis of human leukemias, suggest that overexpression of HB24 in hematopoietic progenitors or T-cells may contribute to oncogenic transformation.

Animals↗
PubMed1993

Prediction of engraftment after peripheral blood stem cell transplantation by CD34-positive cells in grafts.

A total of 91 peripheral blood stem cell collections were performed in 26 children with various malignant tumors and peripheral blood stem cell transplantations (PBSCT) were performed in 15 of the children. There was a positive correlation between logarithm of total CD34+ cells/kg and logarithm of colony-forming unit-granulocyte macrophage (CFU-GM)/kg (r = 0.86). The time elapsed until the white blood cells (WBC) exceeded 1000/microL was related to both CFU-GM (r = 0.67) and CD34+ cell count (r = 0.60). The number of days elapsed until platelet count exceeded 5 x 10(4)/microL was not related to the logarithm of CFU-GM count/10(5) per kg transfused (r = 0.47), but was related to the logarithm of CD34+ cell counts/10(6) per kg transfused (r = 0.73). The number of days elapsed until the reticulocytes exceeded 10% was not related to the logarithm of CFU-GM count/10(5) per kg (r = 0.52), but was related to the logarithm of CD34+ cell counts/10(6) per kg transfused (r = 0.91). Although CD34+ cell counts correlated with the number of CFU-GM, bone marrow regeneration rates in three lineages were predicted more accurately by the number of CD34+ cells transfused than by the number of CFU-GM. These results suggest that measurement of the CD34+ cell count may be useful in predicting bone marrow regeneration rate after PBSCT.

Adolescent↗
PubMed1993

Potential roles for two human homeodomain containing proteins in the proliferation and differentiation of human hematopoietic progenitors.

Two human homeobox genes, HB9 and HLX, are expressed in hematopoietic progenitors and activated lymphocytes. They are implicated in the proliferation of hematopoietic progenitors in response to growth factors and the differentiation of hematopoietic progenitors to mature cell lineages. RNAs from bone marrow cells of patients with acute myeloid or lymphocytic leukemia have high levels of these two genes while similar RNAs from patients with chronic lymphocytic or myeloid leukemias have nearly normal levels. While the significance of these two genes in leukemogenesis is unknown, they are likely to regulate gene transcription during hematopoiesis and their dysregulation may have dire consequences for hematopoietic cells.

Acute Disease↗
PubMed1993

Effects of transgalactosylated disaccharides on the human intestinal microflora and their metabolism.

The effects of transgalactosylated disaccharide (TD) intake on human fecal microflora and their metabolism were investigated in 12 Japanese males. TD is a mixture of sugars, galactosyl galactose, and galactosyl glucose, synthesized from lactose through the transgalactosylation reaction of Streptococcus thermophilus beta-galactosidase. Volunteers took 15 g of the test sugar daily for 6 days. The TD ingestion increased the number of bifidobacteria and lactobacilli, but decreased the number of Bacteroidaceae and Candida spp. in the feces. The ratio of bifidobacteria to total bacteria increased from 0.28 to 0.51. TD decreased the fecal concentrations of propionic acid, isobutyric acid, isovaleric acid, and valeric acid. This sugar also lowered the fecal pH, and the concentrations of fecal ammonia, p-cresol, and indole. Moreover, a positive correlation was found between the concentration of ammonia, and that of branched-chain fatty acids (isobutyric acid and isovaleric acid), p-cresol, and indole. All of these compounds are produced from amino acids through deamination by the intestinal bacteria. The depression of amino acid fermentation by intestinal bacteria may be involved in the reduction of fecal ammonia. These results suggest that a part of the transgalactosylated disaccharides passes into the colon, inducing changes in the colonic microflora composition, hastening carbohydrate fermentation, and depressing amino acid fermentation in the human gut.

Adult↗
PubMed1993

Influence of galactooligosaccharides on the human fecal microflora.

The effects of galactooligosaccharides intake on fecal microflora and their metabolism were investigated in twelve healthy volunteers, in whom the numbers of indigenous bifidobacteria are comparatively low. The galactooligosaccharides ingestion increased the number of bifidobacteria, but remarkable changes of other organisms were not observed. This sugar also lowered fecal nitroreductase activity, the concentrations of indole and isovaleric acid.

Adult↗
PubMed1993

High expression of two diverged homeobox genes, HB24 and HB9, in acute leukemias: molecular markers of hematopoietic cell immaturity.

Homeobox genes encode for sequence-specific DNA-binding proteins which have been implicated in the control of gene expression during development and in certain adult tissues. Two recently characterized human homeobox-containing genes, HB9 and HB24, are known to be expressed in hematopoietic progenitors and to be involved in the regulation of growth and differentiation of progenitor cells to mature hematopoietic cell types. In this study, elevated levels of HB24 and HB9 mRNA expression were detected in bone marrow and peripheral blood mononuclear cells (PBMC) isolated from patients with acute myelogenous or acute lymphocytic leukemia. While the levels of both mRNAs were elevated in all the patients with acute leukemias, the levels of HB9 mRNA were more variable than those of HB24. Immunohistochemical analysis utilizing an HB24 polyclonal antiserum demonstrated elevated levels of HB24 protein in cytopreparations of acute leukemic cells. Nuclear run-on experiments showed that the increases of HB9 and HB24 mRNA transcripts in patients' cells were, at least in part, secondary to increased transcription. The expression of HB9 and HB24 correlated with the clinical status of the patient. No significant level of expression of either HB9 or HB24 was detected in PBMC isolated from patients in remission. In contrast to the findings with cells isolated from patients with acute leukemias, no significant increase in either HB9 or HB24 transcript levels were found in cells from patients with chronic lymphocytic or chronic myelogenous leukemia when compared to normal controls. These findings demonstrate that high levels of HB9 and HB24 expression are common features of acute leukemia and suggest the possibility that the dysregulated expression of these two genes may contribute to leukemogenesis. However, since these two genes are markers of immature hematopoietic cells they may not have an etiologic role in leukemogenesis.

Acute Disease↗
PubMed1993

Establishment of a neuroblastoma cell line and induction of lymphokine-activated killer (LAK) activity against the autologous neuroblastoma cell line.

We have established a new human neuroblastoma (NB) cell line from the bone marrow of a 1-year-old boy with NB, termed JK-NB1, which showed constant growth for as long as 17 months or more, similar phenotype to those of other reported NB cell lines, colony formation in liquid and methylcellulose culture, N-myc amplification, high expression of N-CAM, and NSE production. We have tried to induce LAK cell activity with peripheral blood mononuclear cells (PBMCs) from the patient against the autochthonous JK-NB cells. PBMCs from the patient proliferated up to 20-fold in the presence of interleukin-2 (IL-2) after 9 days of incubation, and LAK activity increased up to 24.7-fold and killed all of the JK-NB1 cells. In contrast, IL-2 alone or PBMCs from the patient or a healthy adult donor had little effect on the growth of NB cells. These data suggest that it is possible to induce LAK cell activity in PBMCs from the patient against autologous as well as allogenic NB cells, and provide a rational base for the clinical use of IL-2 as one of the treatments for NB.

Adrenal Gland Neoplasms↗
PubMed1992

A diverged homeobox gene is involved in the proliferation and lineage commitment of human hematopoietic progenitors and highly expressed in acute myelogenous leukemia.

HB24 is a diverged homeobox gene known to be expressed in hematopoietic progenitor cells. We show here that the inhibition of HB24 expression in CD34+ bone marrow cells via antisense (AS) oligonucleotides impaired the proliferation of these cells in response to interleukin-3 and granulocyte-macrophage colony-stimulating factor. The treatment of CD34+ cells with HB24 AS oligonucleotides also reduced the levels of c-fos, c-myc, c-myb, cyclin B, and p34cdc2 messenger RNAs compared with cells treated with control oligonucleotides. Conversely, the transient transfection of HB24 into a subpopulation of CD34 cells inhibited their differentiation into mature hematopoietic cell types. In addition, HB24 messenger RNA transcripts were elevated in bone marrow and peripheral blood mononuclear cells isolated from patients with acute myelogenous leukemia compared with normal controls. These data suggest that HB24 is an important transcription factor during hematopoietic progenitor proliferation and that differentiation to specific cell types requires its downregulation. Furthermore, dysregulated expression of HB24 impairs the normal differentiation of hematopoietic progenitors and may contribute to leukemogenesis.

Antigens, CD↗
PubMed1992

Stable expression of HB24, a diverged human homeobox gene, in T lymphocytes induces genes involved in T cell activation and growth.

A diverged homeobox gene, HB24, which is known to be induced following lymphocyte activation, was introduced into Jurkat T cells under the control of a constitutive promoter. Stable transfectants of HB24 were established that expressed high levels of HB24 mRNA and possessed an altered phenotype suggestive of activated T cells. A number of genes known to be induced following T cell activation and associated with cell growth were increased in the transfectants, including c-fos, c-myc, c-myb, HLA-DR, lck, NF-kappa B, interleukin-2 and interleukin-2 receptor alpha (IL-2R alpha). Analysis of IL-2R alpha expression by transient transfection of IL-2R alpha promoter constructs into the HB24 transfectants revealed constitutive expression (about 60% of phytohemagglutinin- and phorbol ester-activated Jurkat cells) that was dependent on the kappa B site in the IL-2R alpha promoter. Furthermore, as a consequence of the increased HB24 mRNA levels, the Jurkat HB24 transfectants proliferated more rapidly than control cell lines. Thus, stable expression of HB24 confers an activation phenotype on a human T cell line, implicating this gene as an important transcriptional factor during T cell activation and growth.

Base Sequence↗
PubMed1992

Two diverged human homeobox genes involved in the differentiation of human hematopoietic progenitors map to chromosome 1, bands q41-42.1.

Proteins encoded by homeobox containing genes are sequence-specific DNA binding proteins implicated in the control of gene expression in both developing and adult tissues. Two recently characterized human homeobox genes, HB9 and HB24, are highly expressed in CD34-positive marrow cells but not in CD34-depleted marrow cells. Their expression is readily down-regulated during the differentiation of hematopoietic progenitors to specific cell lineages. In this study, genomic DNA fragments isolated with HB9 (3 kb) and HB24 (6 kb) cDNAs were used to map their chromosomal location by fluorescence in situ hybridization. Both HB9 and HB24 DNA probes gave specific hybridization signals on chromosome 1. The hybridization loci were identified by combining fluorescence images of the probe signals with fluorescence banding patterns generated by cohybridization in situ with an Alu probe (R-like banding) and by DAPI staining (G-like). The results demonstrate that the loci of the HB24 and HB9 genes are within bands 1q41-q42.1. A cohybridization experiment utilizing both probes with two-color fluorescence imaging could not resolve separate loci for the two genes.

Cell Differentiation↗
PubMed1992

Biotransformation of isoeugenol and eugenol by cultured cells of Eucalyptus perriniana.

Three new biotransformation products, eugenyl beta-rutinoside, and isoeugenyl beta-gentiobioside and beta-rutinoside, together with eugenyl beta-glucoside and beta-gentiobioside, and isoeugenyl beta-glucoside, were isolated from jar fermentor culture of Eucalyptus perriniana following administration of eugenol and isoeugenol, respectively. This is the first report of rhamnosylation in a biotransformation catalysed by cultured cells of E. perriniana.

Acetylation↗
PubMed1992

In-vivo blood-brain barrier transport of a novel adrenocorticotropic hormone analogue, ebiratide, demonstrated by brain microdialysis and capillary depletion methods.

The transport of ebiratide, a novel adrenocorticotropic hormone (ACTH) analogue, [H-Met-(O2)-Glu-His-Phe-D-Lys-Phe-NH(CH2)8-NH2], through the blood-brain barrier was directly demonstrated in-vivo. [125I]Ebiratide (16.9 MBq mL-1) or [14C]sucrose (29.2 MBq mL-1) known to be restrictively transported through the blood-brain barrier was infused into the rat internal carotid artery at a flow rate of 50 microL min-1 for 10 min, and after 15 min infusion the distribution volume of each compound in the brain parenchyma was determined by the capillary depletion method. The distribution volume of [125I]ebiratide was 167.8 +/- 62.2 microL (g brain)-1, which was about seven times higher than that of [14C]sucrose (24.9 +/- 4.0 microL g brain)-1, indicating the uptake of ebiratide into brain parenchymal cells. During the infusion into the internal carotid artery, brain microdialysis was simultaneously performed to directly collect the brain interstitial fluid as the dialysate. Radioactivity was detected in the dialysate during the [125I]ebiratide infusion and HPLC analysis of the dialysate revealed that the intact ebiratide accounted for greater than or equal to 80% total radioactivity. The concentrations of [125I]ebiratide and [14C]sucrose in the brain interstitial fluid were estimated based on the relative recovery obtained in the in-vitro recovery study. The brain interstitial fluid/internal carotid arterial blood concentration ratio for [125I]ebiratide was determined to be 1.47 x 10(-2) +/- 0.17 x 10(-2) and was about eight times higher than that for [14C]sucrose (1.92 x 10(-3) +/- 0.36 x 10(-3)), indicating significant transport of ebiratide to the brain interstitial fluid.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1992

Application of ozone disinfection to remove Enterococcus seriolicida, Pasteurella piscicida, and Vibrio anguillarum from seawater.

Survival of bacterial fish pathogens, including Enterococcus seriolicida, Vibrio anguillarum, and Pasteurella piscicida, in ozonated seawater was determined in a batch system. Bacterial counts of all fish pathogens decreased at more than 0.040 to 0.060 mg of total residual oxidants (TROs) per liter, whereas no decrease in viable counts was observed at less than 0.018 to 0.028 mg of TROs per liter. The 99% inactivation point was achieved at concentrations of 0.111 mg/liter for E. seriolicida, 0.063 mg/liter for P. piscicida, and 0.064 mg/liter for V. anguillarum within 1 min. Moreover, the mean 99 and 99.9% killing concentration-contact time (C.t) products were 0.123 and 0.186 mg.min/liter for E. seriolicida, 0.056 and 0.084 mg.min/liter for P. piscicida, and 0.081 and 0.123 mg.min/liter for V. anguillarum, respectively. However, the mean 99 and 99.9% C.t products for the mixed population in coastal seawater were 0.200 and 0.621 mg.min/liter. These results strongly suggest that ozone treatment at more than 1.0 mg of TROs per liter for several minutes is able to disinfect seawater for mariculture efficiently.

Animal Husbandry↗
PubMed1992

Spontaneous increase of transforming growth factor beta production by bronchoalveolar mononuclear cells of patients with systemic autoimmune diseases affecting the lung.

The spontaneous increase in the transcription of the transforming growth factor beta (TGF beta) gene in bronchoalveolar mononuclear cells of patients with autoimmune diseases affecting the lung has been shown by northern blot assay and a nuclear run on transcription assay. Transcription of the TGF beta gene in bronchoalveolar mononuclear cells of patients with autoimmune diseases affecting the lung was increased 10 times compared with normal healthy subjects or patients with bronchial asthma as controls. This observation, confirmed by protein data, suggests that TGF beta, a potent mitogen for fibroblasts, may be produced in bronchoalveolar mononuclear cells during an active immune response in such patients and may be involved in autoimmune related changes of the pathophysiology of cytokine networks when the lung is affected, such as in lung fibrosis.

Blotting, Northern↗
PubMed1992

Acquired T cell specific deficiency other than acquired immunodeficiency syndrome (AIDS).

Evidence of an acquired T cell-specific deficiency distinct from acquired immunodeficiency syndrome (AIDS) in a 63-yr-old Japanese female is provided. Recently, this patients suffered from primary invasive pulmonary aspergillosis. Skin tests to purified protein derivative of tuberculin (PPD) and Aspergillus antigens were negative. Upon admission to our hospital, her lymphocytes were exclusively unresponsive to T cell mitogens (concanavalin A, phytohemagglutinin, and OKT 3). The level of cells defined by monoclonal antibodies (CD1, CD2, CD3, CD4, WT31, and CD5) was less than 3%. In contrast, no decrease in the number of red blood cells, platelets, neutrophils or B cells was apparent. Five years ago, the patient had a normal white blood cell and lymphocyte count. However, over the following 4 yr, she developed lymphopenia. With medication, her pulmonary disease recovered, while lymphopenia still continued. The levels of immunoglobulins, complements and enzyme activities (adenosine deaminase and purine nucleoside phosphorylase) were normal. Moreover, several tests for HIV (ELISA and Western bolt) were negative suggesting that the T cell-specific deficiency was not a congenital immunodeficiency or AIDS but rather a new type of acquired immunodeficiency.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Expression of the HOX-2.3 homeobox gene in human lymphocytes and lymphoid tissues.

Homeobox proteins are sequence-specific DNA-binding proteins initially implicated in the control of gene expression in developing tissues; however, there is increasing evidence that these proteins are important in gene regulation in adult tissues. A cDNA for the homeobox gene HOX-2.3 was isolated from an adult human B-lymphocyte cDNA library. Northern blot analysis showed expression of a 1.1 and a 1.6 kb messenger RNA (mRNA) in a human B-cell line. RNase protection assays demonstrated variable expression in both human B- and T-cell lines. Virally transformed and nontransformed lymphocyte cell lines expressed HOX-2.3 transcripts. Essentially no transcripts were found in unactivated normal B and T lymphocytes; however, B-cell activation with Staphylococcus aureus Cowan strain I and phorbol myristate acetate (PMA) or T-cell activation with phytohemagglutinin and PMA were accompanied by a rapid induction of HOX-2.3 expression even in the presence of the protein synthesis inhibitor, cycloheximide. In situ hybridization was performed to examine HOX-2.3 expression in lymphoid tissues. HOX-2.3 mRNA was detected in the thymic cortex from an 8-year-old child, in the germinal centers in adult tonsil, and in a limited number of hematopoietic cells from the bone marrow. These findings suggest the involvement of HOX-2.3 in regulating gene transcription not only in developing tissues but in hematopoietic and lymphoid tissues as well.

Adult↗
PubMed1991

Selective expression of two homeobox genes in CD34-positive cells from human bone marrow.

Proteins coded by homeobox-containing genes are sequence-specific DNA-binding proteins that have been implicated in the control of gene expression both in developing as well as in adult tissues. Two recently characterized human homeobox genes, HB24 and HB9, were found to be highly expressed in bone marrow cells enriched for CD34-positive cells, present at low levels in unfractionated bone marrow cells, and essentially undetectable in bone marrow cells depleted of CD34 cells. Treatment of CD34-enriched cells with recombinant interleukin-3 (IL-3) and granulocyte macrophage-colony-stimulating factor for 24 hours increased expression of HB24 threefold and HB9 fourfold. Based on studies with actinomycin D, the HB24 and HB9 transcripts in human CD34-positive cells have short half-lives, estimated to be 30 to 45 minutes. Downregulation of HB24 and HB9 expression was found following the treatment of in vitro cultures of CD34-positive cells with IL-3. Thus, the differentiation of CD34-positive cells along a specific cell lineage likely requires downregulation of both HB24 and HB9.

Antigens, CD↗