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Biomedical subjects

A Kaneko

Publications and source records attributed to A Kaneko.

At least 73 records · Page 4Linked to original sources
PubMed2000

The diagnostic value of 123I-IMP SPECT in non-Hodgkin's lymphoma of the central nervous system.

UNLABELLED: N-isopropyl-p-[123I]iodoamphetamine (IMP) SPECT is of low diagnostic value in patients with brain tumors, because brain tumors are visualized as uptake defects. Some reports have described non-Hodgkin's lymphoma of the central nervous system (CNS) as showing high uptake on delayed 123I-IMP SPECT images, suggesting its usefulness in diagnosing CNS lymphoma. In this study, we investigated the clinical value of 123I-IMP SPECT as a diagnostic tool for CNS lymphoma. METHODS: Ninety-six patients with brain tumors, including 12 patients with CNS lymphoma, underwent 123I-IMP SPECT. Eleven patients had primary CNS lymphoma, and 1 had a parenchymal brain metastasis from a breast lymphoma. The total number of lesions was 18, 14 of which were in the cerebral parenchyma, 3 in the brain stem, and 1 in the ventricle. Early SPECT images were initiated 15-30 min after intravenous injection of 111 MBq 123I-IMP, and delayed images were collected 4 h later. SPECT images were visually analyzed with a color-grading scale. Tumor-to-normal activity ratio (T/N) and tumor-to-cerebellum activity ratio (T/C) were calculated for both early and delayed images for semiquantitative analysis. RESULTS: By visual estimation, more than a 3-cm3 volume of CNS lymphoma was detected as an obvious focus of increased accumulation on delayed images. All other brain tumors tested appeared as decreased accumulation on delayed images. T/Ns and T/Cs on delayed images of CNS lymphomas, including tumors less than 3 cm3 in volume, were 1.48+/-0.42 and 1.08+/-0.16, respectively. These ratios in patients with glioma (0.30+/-0.05 and 0.31+/-0.07 respectively) or meningioma (0.34+/-0.10 and 0.41+/-0.17, respectively) showed a significant difference from those in patients with CNS lymphoma (P < 0.0005). CONCLUSION: 123I-IMP SPECT is a helpful tool for diagnosing CNS lymphoma.

Adult↗
PubMed2000

[A case of giant sebaceous gland carcinoma without adequate treatment].

BACKGROUND: A patient with a sebaceous gland carcinoma without adequate treatment is reported. CASE: A 67-year-old man underwent an operation on his left upper eyelid after a diagnosis of chalazion in 1981. Two years after the initial operation, he noticed a tumor in the left upper eyelid. In 1987, he visited another hospital and was diagnosed with sebaceous gland carcinoma by a tissue biopsy. He left it untreated against medical advice. When he visited our hospital in 1996, the tumor was as large as 80 x 75 x 40 mm and the left upper and lower eyelids stuck together. After admission, he died of myocardial infarction 23 days after his visit to our hospital. Autopsy revealed that the tumor had extended into the orbital cavity, paranasal sinus, and base of the skull, with metastasis to the preauricular, submandibular, and cervical lymph nodes and both lungs. The pathology of the tumor was a moderately differentiated sebaceous gland carcinoma. CONCLUSION: This case showed the natural course of extension and metastasis of a sebaceous gland carcinoma.

Aged↗
PubMed1999

Activation by bitter substances of a cationic channel in membrane patches excised from the bullfrog taste receptor cell.

1. The response to bitter-tasting substances was recorded in outside-out membrane patches excised from the taste receptor cell of the bullfrog fungiform papilla. 2. Application of a bitter-tasting substance, quinine or denatonium, induced channel openings under conditions in which none of the second messenger candidates or their precursors (e.g. cyclic nucleotide, inositol 1,4,5-trisphosphate, Ca2+, ATP and GTP) were present on either side of the membrane. The response could be recorded > 10 min after excision of the patch membrane. These data suggest that the channel was directly gated by the bitter-tasting substances. 3. No change in response was detected upon addition to the cytoplasmic side of either GDPbetaS (1 mM) or GTPgammaS (1 mM), suggesting that the G protein cascade has no direct relation to response generation. 4. The quinine-induced current was dose dependent. The lowest effective concentration was approximately 0.1 mM, and the saturating concentration was near 1 mM. The dose-response curve was fitted by the Hill equation with a K of 0.52 mM and a Hill coefficient of 3.8. 5. The single channel conductance measured in 120 mM NaCl solution was 10 pS. The channel was cation selective, and the ratio of the permeabilities for Na+, K+ and Cs+ (PNa : PK : PCs) was 1 : 0.48 : 0.39. The unitary conductance was dependent on the extracellular Ca2+ concentration ([Ca2+]o); 9.2 pS in a nominally Ca2+-free solution, and 4.5 pS in 1. 8 mM [Ca2+]o. 6. The dose dependence, the ion selectivity and the dependence of the unitary conductance on [Ca2+]o were almost identical to those of the quinine-induced whole-cell current reported previously, indicating that the channel activity observed in the excised membrane is the basis of the whole-cell current. 7. The present observations suggest the new possibility that the cationic channel directly gated by bitter substances is involved in the bitter taste transduction mechanism.

Animals↗
PubMed1999

Differential effects of human granulocyte colony-stimulating factor (hG-CSF) and thrombopoietin on megakaryopoiesis and platelet function in hG-CSF receptor-transgenic mice.

Granulocyte-colony stimulating factor (G-CSF) has been found to act on the neutrophilic lineage. We recently showed that human G-CSF (hG-CSF) has effects similar to early-acting cytokines such as interleukin-3 (IL-3) in the development of multipotential hematopoietic progenitors in transgenic (Tg) mice expressing receptors (R) for hG-CSF. In the present study, we examined the effects of hG-CSF on more mature hematopoietic cells committed to megakaryocytic lineage in these Tg mice. The administration of hG-CSF to the Tg mice increased the numbers of both platelets in peripheral blood and megakaryocytes in the spleen, indicating that hG-CSF stimulates megakaryopoiesis in the Tg mice in vivo. The stimulatory effect of hG-CSF was also supported by the results of studies in vitro. hG-CSF supported megakaryocyte colony formation in a dose-dependent fashion in clonal cultures of bone marrow cells derived from the Tg mice. Direct effects of hG-CSF on megakaryocytic progenitors in the Tg mice were confirmed by culture of single-cell sorted from bone marrow cells. hG-CSF showed a stronger effect on maturation of megakaryocytes in the Tg mice than that of IL-3 alone, but weaker than that of TPO alone. In addition, hG-CSF induced phosphorylation of STAT3 but not Jak2 or STAT5, while TPO induced phosphorylation of both. In contrast to TPO, hG-CSF did not enhance ADP-induced aggregation. Thus, hG-CSF has a wide variety of functions in megakaryopoiesis of hG-CSFR-Tg mice, as compared with other megakaryopoietic cytokines, but the activity of hG-CSF in megakaryocytes and platelets does not stand up to a comparison with that of TPO. Specific signals may be required for the full maturation and activation of platelets.

Animals↗
PubMed1999

CD4+ and/or gammadelta+ T cells in the liver spontaneously produce IL-4 in vitro during the early phase of Leishmania major infection in susceptible BALB/c mice.

Numerous studies on the cytokine production profile in Leishmania major infected susceptible and resistant mice have been carried out to elucidate the mechanisms of healing or non-healing of this infection. However, many methods may have failed to detect the actual cytokine production in the inflammatory foci. To overcome this problems, the ELISPOT assay was used to examine the spontaneous production of IL-4 and IFN-gamma in vitro by mononuclear cells from the spleen, lymph nodes and liver in L. major-infected susceptible BALB/c and resistant C57BL/6 mice. None of these mononuclear cells spontaneously produced IFN-gamma in either mouse strains in vitro in the absence of the corresponding antigen(s). However, liver mononuclear cells from infected BALB/c mice spontaneously produced IL-4 in vitro in as early as 2 weeks after the infection, but this was not observed in C57BL/6 mice. The IL-4 producing liver lymphocytes consisted of CD4+ and/or gammadelta+ T cells and uncharacterized cells. These results suggest that liver lymphocytes play some role in the establishment of Th2 prevalence in susceptible BALB/c mice, based on the importance of IL.4 production in the early phase of L. major infection in establishing Th2 dominance in this parasite susceptible mouse.

Animals↗
PubMed1999

Functional interaction between Oct-1 and retinoid X receptor.

The retinoid X receptor (RXR) is a member of the nuclear hormone receptor superfamily and heterodimerizes with a variety of other family members such as the thyroid hormone receptor (TR),1 retinoic acid receptor, vitamin D receptor, and peroxisome proliferator-activated receptor. Therefore, RXR is supposed to play a key role in a ligand-dependent regulation of gene transcription by nuclear receptors. In this study, we have identified the octamer-binding transcription factor-1 (Oct-1) as a novel interaction factor of RXR. In vitro pull-down assays using RXR deletion mutants showed that the interaction surfaces were located in the region encompassing the DNA binding domain (C domain) and the hinge domain (D domain) of RXR. We also showed that RXR interacted with the POU homeodomain but not with the POU-specific domain of Oct-1. Gel shift analysis revealed that Oct-1 reduced the binding of TR/RXR heterodimers to the thyroid hormone response element (TRE). In transient transfection assays using COS1 cells, Oct-1 repressed the T3-dependent transcriptional activity of TR/RXR heterodimers, consistent with in vitro DNA binding data; however, transcriptional activation by Gal4-TR(LBD) (LBD, ligand binding domain), which lacks its own DNA binding domain but retains responsiveness to T3, was not influenced by Oct-1. These results suggest that Oct-1 functionally interacts with RXR and negatively regulates the nuclear receptor signaling pathway by altering the DNA binding ability of the receptors.

Animals↗
PubMed1999

Characterization of mast cell-committed progenitors present in human umbilical cord blood.

Human mast cells are derived from CD34(+) hematopoietic cells present in cord blood, bone marrow, and peripheral blood. However, little is known about the properties of the CD34(+) cells. We demonstrated here that mast cell progenitors that have distinct phenotypes from other hematopoietic cell types are present in cord blood by culturing single, sorted CD34(+) cells in 96-well plates or unsorted cells in methylcellulose. The CD34(+) mast cell-committed progenitors often expressed CD38 and often lacked HLA-DR, whereas CD34(+) erythroid progenitors often expressed both CD38 and HLA-DR and CD34(+) granulocyte-macrophage progenitors often had CD33 and sometimes expressed CD38. We then cultured single cord blood-derived CD34(+)CD38(+) cells under conditions optimal for mast cells and three types of myeloid cells, ie, basophils, eosinophils, and macrophages. Of 1,200 CD34(+)CD38(+) cells, we were able to detect 13 pure mast cell colonies and 52 pure colonies consisting of either one of these three myeloid cell types. We found 17 colonies consisting of two of the three myeloid cell types, whereas only one colony consisted of mast cells and another cell type. These results indicate that human mast cells develop from progenitors that have unique phenotypes and that committed mast cell progenitors develop from multipotent hematopoietic cells through a pathway distinct from myeloid lineages including basophils, which have many similarities to mast cells.

ADP-ribosyl Cyclase↗
PubMed1999

1,25-Dihydroxyvitamin D3 suppresses the expression of the VCAM-1 receptor, VLA-4 in human leukemic HL-60 cells.

Very late antigen-4 (VLA-4) is the complex with alpha4 and beta1 integrins, which is the receptors to fibronectin and VCAM-1. We evaluate the effect of 1,25(OH)2D3 on the expression of VLA-4 in human leukemic HL-60, U937 cells and human melanoma A375 cells. Flow cytometric analysis demonstrate that the expression of alpha4 integrin is negatively regulated in the cell lines we studied. The expression of beta1 integrin is also decreased in HL-60 and U937 cells. The mRNA expression of alpha4 integrin is significantly decreased by the treatment with 1,25(OH)2D3, whereas 1,25(OH)2D3 does not alter the expression of beta1 mRNA. The adhesion assay demonstrate that the number of adherent cells treated with 1, 25(OH)2D3 is significantly lower than that untreated on VCAM-1-coated wells. Because VCAM-1 is highly expressed in the endothelial cells, it is possible that 1,25(OH)2D3 prevents the attachment of the cells from the endothelial cells in vivo.

Antigens, CD↗
PubMed1999

Evidence for neural regulation of inflammatory synovial cell functions by secreting calcitonin gene-related peptide and vasoactive intestinal peptide in patients with rheumatoid arthritis.

OBJECTIVE: To elucidate the possible involvement of the nervous system in the regulation of pathophysiologic responses in patients with rheumatoid arthritis (RA), we examined the expression of peripheral nerves containing the neuropeptides calcitonin gene-related peptide (CGRP) and vasoactive intestinal peptide (VIP) in RA synovium and their effects on RA synovial cell functions. METHODS: The effects of CGRP and VIP on proinflammatory cytokine and matrix metalloproteinase (MMP) production by RA synovial cells were estimated by enzyme-linked immunosorbent assay, and their messenger RNA (mRNA) expression by reverse transcription-polymerase chain reaction (RT-PCR) using limiting dilutions of the complementary DNA. Expression of CGRP receptors (CGRPRs) and VIP receptors (VIPRs) on RA synovial cells was assessed by RT-PCR and radioreceptor assays. The functions of CGRPRs and VIPRs of the synovial cells were studied by using a CGRPR antagonist and a VIPR antagonist, respectively. RESULTS: CGRP and VIP inhibited the proliferation of, and the proinflammatory cytokine and MMP production by, RA synovial cells at the level of mRNA expression. Expression of CGRPR and VIPR on RA fibroblast-like synovial cells was confirmed by RT-PCR and radioreceptor assays. Functions of the neuropeptide receptors were inhibited by their receptor antagonists. CGRP and VIP inhibited nuclear translocation and phosphorylation of the transcription factor cAMP response element binding protein in RA synovial cells. CONCLUSION: CGRP and VIP inhibited excessive synovial cell functions, which suggests neural regulation of inflammatory responses in patients with RA and possible clinical application of the neuropeptides.

Adult↗
PubMed1999

Adrenaline enhances odorant contrast by modulating signal encoding in olfactory receptor cells.

Olfactory perception is influenced by hormones. Here we report that adrenaline can directly affect the signal encoding of olfactory receptor cells. Application of adrenaline suppressed action potentials near threshold and increased their frequency in response to strong stimuli, resulting in a narrower dynamic range. Under voltage-clamp conditions, adrenaline enhanced sodium current and reduced T-type calcium current. Because sodium current is the major component of spike generation and T-type calcium current lowers the threshold in olfactory receptor cells, the effects of adrenaline on these currents are consistent with the results obtained under current-clamp conditions. Both effects involved a common cytoplasmic pathway, cAMP-dependent phosphorylation. We suggest that adrenaline may enhance contrast in olfactory perception by this mechanism.

Action Potentials↗
PubMed1999

Urease-positive thermophilic strains of Campylobacter isolated from seagulls (Larus spp.).

Three strains of urease-positive thermophilic Campylobacter (UPTC), designated A1, A2 and A3, were identified by biochemical characterization after isolation from faeces of seagulls in Northern Ireland in 1996. The biochemical characteristics of the strains were identical to those of strains described previously. Analysis by pulsed-field gel electrophoresis (PFGE) after separate digestion with ApaI and SmaI demonstrated that the respective PFGE profiles were indistinguishable. The PFGE analysis also suggested that the genomes were approximately 1810 kb in length. This is the first example of the isolation of UPTC from flying homoiothermal animals, i.e. from seagulls (Larus spp.).

Animals↗
PubMed1999

Intrinsic efficacy of proguanil against falciparum and vivax malaria independent of the metabolite cycloguanil.

Mutations in human CYP2C19 and parasite dihydrofolate reductase (dhfr) genes, related to poor metabolism of proguanil and resistance to cycloguanil, respectively, have both been assumed to be associated with poor antimalarial effect by proguanil. To study this, 95 subjects with uncomplicated Plasmodium falciparum or Plasmodium vivax infections in Vanuatu received proguanil treatment for 3 days (adult relative dose of 300-500 mg/day) and were followed up for 28 days. A similarly high antimalarial efficacy against both infections was observed in 62 patients with CYP2C19-related poor metabolizer genotype and in 33 with extensive metabolizer genotype, even though blood cycloguanil was significantly more often detected in those with extensive metabolizer genotype than in those with poor metabolizer genotype. All 28 P. falciparum isolates had two dhfr mutations (residues 59 and 108), suggesting moderate resistance to cycloguanil. The results suggest that the parent compound proguanil has significant intrinsic efficacy against falciparum and vivax malaria independent of the metabolite cycloguanil.

Adolescent↗
PubMed1999

Chimeric cytokine receptor can transduce expansion signals in interleukin 6 receptor alpha (IL-6Ralpha)-, IL-11Ralpha-, and gp130-low to -negative primitive hematopoietic progenitors.

We generated transgenic mice expressing chimeric receptors, which comprise extracellular domains of the human granulocyte-macrophage colony-stimulating factor (hGM-CSF) receptor and transmembrane and cytoplasmic domains of the mouse leukemia inhibitory factor receptor. In suspension cultures of lineage-negative (Lin(-)), 5-fluorouracil-resistant bone marrow cells of the transgenic mice, a combination of hGM-CSF and stem cell factor (SCF) induced exponential expansions of mixed colony-forming unit. The combination of hGM-CSF and SCF was effective on enriched, Lin(-)Sca-1(+)c-kit(+) progenitors and increased either mixed colony-forming unit or cobblestone area-forming cells. In case of stimulation with hGM-CSF and SCF, interleukin-6 (IL-6) and SCF, or IL-11 and SCF, the most efficient expansion was achieved with hGM-CSF and SCF. When Lin(-)Sca-1(+)c-kit(+)CD34(-) further enriched progenitors were clone sorted and individually incubated in the presence of SCF, hGM-CSF stimulated a larger number of cells than did IL-6, IL-6 and soluble IL-6 receptor (IL-6R), or IL-11. These data suggest the presence of IL-6Ralpha-, IL-11Ralpha-, and gp130-low to -negative primitive hematopoietic progenitors. Such primitive progenitors are equipped with signal transduction molecules and can expand when these chimeric receptors are genetically introduced into the cells and stimulated with hGM-CSF in the presence of SCF.

Animals↗
PubMed1999

TTG as the initiation codon of Salmonella slyA, a gene required for survival within macrophages.

The slyA gene, which has been implicated in the virulence of Salmonella serovar Typhimurium and its survival in macrophages, is widely distributed among different Salmonella serovars. In this study, we cloned and sequenced the translational initiation region of the slyA gene from nine different serovars and found sequence differences in the previously proposed ATG initiation codon but not in a TTG triplet, another putative initiation codon in the slyA gene. Therefore, we determined the actual translational initiation site of the slyA gene by analyzing slyA genes with defined mutation in either the ATG or TTG sequences in an in vitro translation assay and a quantitative hemolytic assay in Escherichia coli. The replacement of TTG by TTC in the slyA gene significantly reduced both the amount of protein synthesized and the hemolytic activity of a transformed strain of E. coli, while replacement of ATG by ATC had no effect in these assays. In addition, the amino acid sequence analysis of the His-tagged SlyA protein showed that it was identical with the amino acid sequence deduced from the 5' end of the slyA gene with a TTG initiation codon. Our results suggest that TTG serves as the translational initiation codon for the slyA gene of Salmonella.

Amino Acid Sequence↗
PubMed1999

Characterization of two novel retinoic acid-resistant cell lines derived from HL-60 cells following long-term culture with all-trans-retinoic acid.

Either all-trans-retinoic acid (RA) or vitamin D3 (VD) induces differentiation of the myeloid leukemia cell line HL-60. RA is available for the treatment of acute promyeloleukemia, although the development of resistance to the agent is a serious problem for differentiation-inducing therapy. To approach the mechanisms of resistance to RA, we developed two novel cell lines, HL-60-R2 and R9, which were subcloned after exposure to increasing concentrations of RA. The growth rate of HL-60-R2 cells was significantly increased by RA treatment, whereas the growth rate of HL-60-R9 was not affected. RA induces apoptosis in the parental HL-60 cells. The number of apoptotic cells, however, was not increased and nitroblue tetrazolium (NBT) reduction was not altered by 1 microM RA in either of the cloned cell lines. Treatment with VD induced monocytic differentiation and increased the expression of CD11b in HL-60 and HL-60-R9 cells, but not in HL-60-R2 cells. Flow cytometric and G-banding analysis demonstrated that R2 cells were near-triploid. The sequencing analysis revealed a deletion of three nucleotides in the sequence of the RAR alpha gene in HL-60-R9 cells, resulting in deletion of codon 286. No mutation was found in HL-60-R2 cells. Taken together, these data indicate that the resistance to RA is caused by the mutation in RAR alpha of HL-60-R9, but by other factor(s), which also affect the VD-response pathways, in HL-60-R2. The abnormal response to VD may be associated with the abnormal ploidy of the R2 cells.

Antineoplastic Agents↗