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Biomedical subjects

T Nakano

Publications and source records attributed to T Nakano.

At least 217 records · Page 12Linked to original sources
PubMed2000

Release of a product of growth arrest-specific gene 6 from rat platelets.

A product of growth arrest-specific gene 6 (Gas6) is known to be synthesized by growth-arrested cells. In this study, we found that several rat tissues including platelets contain Gas6 and activation of the platelets with thrombin provoked the release of Gas6. ADP and collagen, which as well as thrombin stimulated release of ATP from platelets, also enhanced the release of Gas6, suggesting that the mechanism of its release was similar to that of ATP release. This study provides the first evidence of growth arrest-independent secretion of Gas6 and suggests the involvement of Gas6 in vascular diseases as well as hemostasis.

Adenosine Diphosphate↗
PubMed2000

OTX2 directly interacts with LIM1 and HNF-3beta.

Otx2 is a paired-class homeobox gene, and its functions in anterior visceral endoderm and/or anterior mesendoderm have been suggested to be vital for head development in mammals. Several transcription factors are expressed in these tissues, and mutant mice analyses have suggested the interactions of the Otx2 gene cascade with the Lim1 or HNF-3beta cascade. Here we show that OTX2 directly associates with LIM1 and HNF-3beta; OTX2 binds to the LIM1 homeodomain (HD) with its C-terminal region, whereas both HD and C-terminal regions of OTX2 bind to the HNF-3beta fork head domain or OTX2 HD. The luciferase assay with the P3C sequence, a specific DNA binding sequence for paired-class homeobox genes, has demonstrated that LIM1 enhances, but HNF-3beta represses, OTX2-directed gene expression. Direct interactions of OTX2 with LIM1 or HNF-3beta may play important roles in anterior visceral endoderm and/or anterior mesendoderm to constitute transcriptional regulatory networks for head development.

Animals↗
PubMed2000

Inhibitory interaction of c-Myb and GATA-1 via transcriptional co-activator CBP.

Gene targeting experiments have revealed that transcription factors such as c-Myb and GATA-1 play crucial roles during hematopoietic differentiation. c-Myb is necessary in the immature cells of almost every hematopoietic lineage and GATA-1 is essential for the development of the erythroid lineage. In addition, CREB-binding protein (CBP) acts as a transcriptional adapter for various transcription factors, including c-Myb and GATA-1. In this paper, we show that the transcription factors c-Myb and GATA-1 each inhibit the transcriptional activity of the other and that any possible bipartite complexes c-Myb, GATA-1, and CBP could be formed, but the tripartite complex was hardly formed. The exclusive binding of GATA-1 and c-Myb to CBP is probably the molecular basis for the mutual inhibition of their transcriptional activity. Our data suggest that cross-talk between these three factors might be important for hematopoietic differentiation and that CBP functions as a key molecule during the process.

Animals↗
PubMed2000

Angiogenesis inhibition by transdominant mutant Ets-1.

The expression of transcription factor Ets-1 is induced in endothelial cells (ECs) by angiogenic factor; and in turn Ets-1 converts ECs to angiogenic invasive phenotype. In order to control angiogenesis, we constructed a transdominant mutant Ets-1 (TMEts-1) which acts as a dominant negative molecule. This molecule inhibited the DNA binding and the transactivation activity of the wild-type Ets-1. Stable transfection of murine endothelial cell line MSS31 cells with the TMets-1 gene impaired angiogenic activities including proliferation, migration, invasion, and tube formation in type-1 collagen gel. Finally, we incorporated the TMets-1 gene into a non-proliferative adenovirus vector, designated as AdTMets-1. AdTMets-1 significantly inhibited angiogenesis in the Matrigel plugs injected into the subcutaneous tissue of C57BL mice. These results indicate that TMets-1 would be a tool for angiogenic inhibition.

3T3 Cells↗
PubMed2000

Signal transduction and transcriptional regulation of angiogenesis.

When quiescent endothelial cells (ECs) are exposed to angiogenic factor such as VEGF; ECs express proteases to degrade extracellular matrices, migrate, proliferate and form new vessels. However, the molecular mechanism of these events is not fully characterized yet. We are studying the signal transduction and transcriptional regulation of angiogenesis. We investigated the properties of two VEGF receptors, Flt-1 and KDR, by using two newly developed blocking monoclonal antibodies (mAbs), i.e., anti-human Flt-1 mAb and anti-human KDR mAb. VEGF elicited induction of transcription factor Ets-1 in human umbilical vein endothelial cells (HUVECs). This induction was mediated by the KDR/Flt-1 heterodimer and the KDR homodimer. The role of transcription factor Ets-1 in angiogenesis was further clarified. We established both high and low Ets-1 expressing EC lines, and compared angiogenic properties of these cell lines with a parental murine EC line, MSS31. The growth rate was almost identical among three cell lines. It appeared that gene expressions of matrix metalloproteinases (MMP-1, MMP-3, and MMP-9) as well as integrin beta 3 were correlated with the level of Ets-1 expression. As a result, the invasiveness was enhanced in high Ets-1 expressing cells and reduced in low Ets-1 expressing cells compared with parental cells, and high Ets-1 expressing cells made more tube-like structures in type 1 collagen gel. These results indicate that Ets-1 is a principle transcription factor converting ECs to the angiogeneic phenotype.

Animals↗
PubMed2000

A case of malignant lymphoma of the hand.

Malignant lymphoma is rarely seen in the hand. We present a case of malignant lymphoma of the hand with Ga-67 citrate and MR images, and discuss the usefulness of Ga-67 citrate scintigraphy for diagnosing this condition.

Aged↗
PubMed2000

Novel chimeric p16 and p27 molecules with increased antiproliferative activity for vascular disease gene therapy.

We describe the construction and characterization of a series of novel cyclin-dependent kinase inhibitors with increased antiproliferative activity for use in the genetic treatment of hyperproliferative cell disorders, such as angioplasty-induced restenosis. These inhibitors were generated through the fusion of truncated versions of the p27 gene to the full-length p16 gene. Biochemically, the p27-p16 chimeric molecules were of comparable potency to the parental p27 in inhibiting the activities of several cyclin-dependent kinases in vitro. Replication-deficient adenoviruses encoding the parental p16, p27 genes, or their derivatives were created to assess the potency of the novel cyclin-dependent kinase inhibitor chimeric molecules to inhibit vascular smooth muscle cell proliferation, which is the seminal event in the restenosis process. One of the p27-p16 chimeric molecules, W9, was observed to be the most potent inhibitor of human primary smooth muscle and endothelial cell proliferation when compared to the p16, p27, p27 derivatives or several alternative p27-p16 chimeric molecules. Overexpression of the W9 chimeric molecule in human coronary artery smooth muscle cells induced human coronary artery smooth muscle cell growth arrest in G1 but did not induce cell apoptosis. Recombinant adenoviral vectors that express this W9 chimeric cyclin-dependent kinase inhibitor molecule constitute a novel potent antiproliferative agent for the treatment of restenosis.

Adenoviridae↗
PubMed2000

Detection of viable cortical neurons using benzodiazepine receptor imaging after reversible focal ischaemia in rats: comparison with regional cerebral blood flow.

To elucidate the utility of benzodiazepine receptor imaging for the detection of viable cortical neurons, dual-tracer autoradiography using iodine-125 iomazenil (IMZ) and iodine-123 N-isopropyl-4-iodoamphetamine (IMP) was performed in a model of reversible focal ischaemia during the acute and subacute phases. The right middle cerebral artery of anaesthetized rats was occluded for 60 min using an intraluminal filament and reperfused. In the acute phase study, 125I-IMZ (370 kBq) was injected via the femoral vein at 2 h after reperfusion, and 123I-IMP (37 MBq) was injected at 50 min post-injection. Rats were sacrificed 10 min after the injection of 123I-IMP. In the subacute phase study, the same procedure was performed at 5 days after reperfusion. In the acute phase, the IMP uptake was significantly decreased in almost all areas of the lesioned hemisphere, an exception being the cerebellum; however, the IMZ uptake was significantly decreased only in ischaemic cores. The discrepancy between IMZ and IMP uptake was observed in the lateral neocortex and the lateral caudate putamen (CPu), which were most frequently damaged in this ischaemic model. In the subacute phase, the IMZ uptake in lesioned rats was significantly decreased only in the parietal lobe and hippocampus, though the IMP uptake was decreased in many regions of lesioned hemispheres (the frontal, parietal cortex, CPu, hippocampus and thalamus). Histopathological findings indicated that both the IMP and the IMZ uptake was markedly decreased in necrotic areas. Although the IMP uptake was significantly decreased in the ischaemic areas, the IMZ uptake was maintained in these areas. These results suggest that benzodiazepine receptor imaging is superior to regional cerebral blood flow imaging for the detection of viable cortical neurons in both the acute and subacute phases of ischaemia.

Animals↗
PubMed2000

Abnormal information processing in dementia of Alzheimer type. A study using the event-related potential's field.

Electrical field changes of event-related potentials (ERPs) were investigated in 26 patients with dementia of Alzheimer's type (DAT) and 12 age-matched normal subjects. The patients were assessed with the Clinical Dementia Rating and Mini-Mental State. Each patient selected had only mild to moderate mental disability. Auditory oddball stimulation was presented at 1.5 s intervals and 1,000 Hz for the nontarget and 2,000 Hz for the target tones, both at 85 dB. The target tones were 20% of all the tones. The reference-independent data (latency, global field power: GFP, dissimilarity index: DISS and location of centroids) were obtained and analyzed for each ERP component. The momentary electric strength or 'hilliness' of the ERPs landscape was indicated by GFP. The patients showed prolonged latencies and decreased P300 GFP amplitudes and of N100 GFP. These findings suggest that the abnormal electrical field of ERP may reflect abnormal information processing following the attentional process for target stimuli in DAT patients.

Aged↗
PubMed2000

Treatment of dark-grown Arabidopsis thaliana with a brassinosteroid-biosynthesis inhibitor, brassinazole, induces some characteristics of light-grown plants.

When a brassinosteroid biosynthesis inhibitor, brassinazole (Brz), was applied at concentrations ranging from 0.1 to 2 microM. Arabidopsis thaliana (L.) Heynh seedlings grown in the dark exhibited morphological features of light-grown plants, i.e. short hypocotyls, expanded cotyledons, and true leaves, in a dose-dependent manner. Control (non Brz-treated) seedlings grown in the dark for 40 d did not develop leaf primordia. However, treatment with the lowest concentration of Brz induced the development of leaf buds, although it hardly induced any short hypocotyls, and treatment with the highest concentration of Brz induced both short hypocotyls and leaves. Labeling experiments with the thymidine analogue 5-bromo-2'-deoxyuridine revealed that amplification of cell nuclei and organellar nucleoids is activated in the shoot apical meristems of dark-grown Brz-treated seedlings. These results suggest that Brz-treatment induces development of true leaves. Furthermore, condensation and scattering of plastid nucleoids, which is known to occur during the differentiation of etioplasts into chloroplasts, was observed in the plastids of dark-grown Brz-treated cotyledons. In addition, high levels of ribulose-1,5-bisphosphate carboxylase-oxygenase proteins accumulated in the plastids of the cotyledons. Electron microscopy showed that the plastids were etioplasts with a prolamellar body and few thylakoid membranes. These results suggest that Brz treatment in the dark induces the initial steps of plastid differentiation, which occur prior to the development of thylakoid membranes. This is a novel presumed function of brassinosteroids. These cytological changes seen in Brz-treated Arabidopsis were exactly the same as those seen in a brassinosteroid-biosynthesis-deficient mutant, det2, supporting the hypothesis that Brz has no side-effects except inhibiting brassinosteroid biosynthesis, and should prove a useful tool in clarifying the role of brassinosteroids.

Arabidopsis↗
PubMed2000

Serum CYFRA 21-1 in cervical cancer patients treated with radiation therapy.

BACKGROUND: A fragment of cytokeratin 19, referred to as CYFRA 21-1, is abundant in the serum of many patients with malignant tumors and is recognized as one of the established tumor markers, especially for non-small-cell lung cancer. In this study, the clinical usefulness of CYFRA 21-1 was investigated in cervical cancer patients treated with radiation therapy with reference to squamous-cell-carcinoma-related antigen (SCC-Ag), a common tumor marker of cervical squamous cell carcinoma. MATERIALS AND METHODS: The serum levels of CYFRA 21-1 and SCC-Ag of 50 patients with squamous cell carcinoma of the uterine cervix were measured before and after radiation therapy. RESULTS: CYFRA 21-1 was positive in 52% of the patients. The incidence increased with the stage of the cancer, and post-treatment increases were a sign of disease progression. During radiation, serum levels of CYFRA 21-1 decreased significantly and reflected the radiation effect well. In addition, CYFRA 21-1 was negative in all patients without distant metastasis at the end of radiation therapy. Compared with SCC-Ag, patients were less often positive for CYFRA 21-1, but there was a statistically positive correlation between the two markers (correlation matrix=0.69). CONCLUSIONS: CYFRA 21-1 can be used in monitoring the outcome of patients with squamous cell carcinoma of the uterine cervix. It may be particularly useful for patients without SCC-Ag.

Adult↗
PubMed2000

Comparative ultrastructure of eggs in Echinostoma paraensei, E. caproni, and E. trivolvis (Trematoda: Echinostomatidae).

The 37-collar-spined echinostomes Echinostoma paraensei, E. caproni, and E. trivolvis are digeneans that live in the intestine of small mammals and birds. Comparative studies of the eggs of these species were done using light microscopy (LM), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The egg of E. caproni was the largest of the three species studied, whereas the egg of E. trivolvis was the smallest in both length and width. The SEM study showed differences in the aboperculum region of the eggs in all three species. The TEM study showed that the eggshell of all three species consisted of three layers, but no difference in eggshell structure was observed in any species.

Animals↗
PubMed2000

Factors correlated with fatigue in disease-free breast cancer patients: application of the Cancer Fatigue Scale.

Fatigue is one of the most frequent symptoms in cancer patients. However, the precise causes of this fatigue are still unknown, and this situation makes it difficult to combat the problem. The present study was conducted to investigate factors correlated with fatigue in disease-free breast cancer patients. A group of 134 randomly selected ambulatory breast cancer patients who had undergone successful surgical treatment participated. They completed the Cancer Fatigue Scale, the Hospital Anxiety and Depression Scale, the Mental Adjustment to Cancer Scale, and an ad hoc questionnaire detailing physical symptoms, social support, and demographic variables at home and returned them by mail the following day. Multiple regression analysis revealed that fatigue was significantly correlated with dyspnea, insufficient sleep, and depression, and that these three variables accounted for a total of 46% of variance in fatigue. Factors concerned with the cancer and treatment, such as disease stage, lymph node metastasis, number of days since operation, past intravenous chemotherapy, radiotherapy, current use of fluoropyrimidine compounds, and current use of tamoxifen citrate were not correlated with fatigue. The results suggest that fatigue in this population is determined by current physical and psychological distress rather than by the cancer itself and prior cancer treatments, and that the management of dyspnea, insomnia, and depression might be important in reducing fatigue in this population.

Adult↗
PubMed2000

Identification of a novel 23kDa protein encoded by putative open reading frame 2 of TT virus (TTV) genotype 1 different from the other genotypes.

We report the entire open reading frames (ORFs) sequences of four TT virus (TTV) isolates, one genotype 2 (G2) and three G4 isolates. Despite a DNA virus, TTV possesses high rate of amino acid (aa) substitution: the aa sequence homology of ORF1 and 2 is lower than the nucleotide homology. The partial 'N22' region of ORF1 is suitable for genotyping of 'prototype TTV' isolates, because the phylogenetic tree from partial 'N22' sequence is consistent with that from the entire ORF1. Based on our sequence data, ORF2 from most isolates excluding G1 encode truncated 49 aa (pORF2a) because of an in-frame stop codon, although ORF2s from most G1 isolates encode 202 aa (pORF2ab). Just downstream the stop codon, another ORF encoding a protein of approximately 150 aa (pORF2b) is found, whose homology is quite low among these genotypes. Our in vitro transcription/translation study supports that all G1a and a part of G b without an in-frame stop codon dominantly encode pORF2ab, a novel 23 kDa protein, whereas the other genotypes with an in-frame stop codon encode pORF2b (17 kDa). Our data indicate TTV G1a and a part of G1b should have different characteristics from the other genotypes.

Amino Acid Sequence↗
PubMed2000

Oral glucose retention, saliva viscosity and flow rate in 5-year-old children.

There are significant differences of glucose retention in site-specificity and individuals. Sixty-two 5-year-old nursery schoolchildren participated in this study on the relation between the viscosity of saliva and flow rate and glucose retention. Each child was instructed to rinse his/her mouth with a glucose solution (0.5 M, 5 ml) and then to spit out. Three minutes after rinsing, glucose retention was determined. Resting saliva was collected by a natural outflow method, then the flow rate was determined. A rotational viscometer was used to determine the viscosity. Glucose retention and flow rate were correlated at the left maxillary primary molars, and glucose retention and viscosity were correlated at the maxillary central primary incisors. It was concluded that glucose retention after glucose mouth rinsing was site-specific, and that glucose retention and the index of decayed, missing and filled primary teeth (dmft) were slightly correlated with the salivary viscosity and flow rate.

Analysis of Variance↗
PubMed2000

Relation between RLP-triglyceride to RLP-cholesterol ratio and particle size distribution in RLP-cholesterol profiles by HPLC.

Remnant-Like Particles (RLP) isolated by an immunoseparation method are heterogeneous in their physical and biochemical properties. The objective of this study was to examine the relation between RLP-triglyceride (RLP-TG) to RLP-cholesterol (RLP-C) ratio and particle size distribution in RLP-C profiles from patients with hyperlipoproteinemia by HPLC. RLP were isolated from serum samples from 147 subjects. RLP-C and RLP-TG were quantified by respective enzymatic methods. Particle sizes of the RLP were measured using HPLC with 4 connected TSKgel LipopropakXL columns. Based on HPLC profiles of RLP-C from individual subjects, three different types were classified: predominantly LDL, predominantly VLDL, and mostly VLDL types. All patients with type III hyperlipidemia were mostly VLDL type but with smaller particle size of VLDL (32 nm) than other subjects. Severe hypertriglyceridemic (TG>4.52 mmoll(-1)) subjects were mostly VLDL type with large particle size (41 nm). As for all subjects (n=105) without predominantly LDL type, a significant correlation between RLP particle size and RLP-TG to RLP-C ratio (r=0. 432, P<0.001) was obtained, but not in case of serum TG to RLP-C ratio (r=0.062). It suggests that RLP-TG to RLP-C ratio might be used for discrimination of atherogenic smaller-sized lipoprotein from larger-sized TG-rich lipoprotein remnants.

Apolipoproteins↗
PubMed2000

Contrast-enhanced immunoelectron microscopy for Helicobacter pylori.

Since a method of contrast enhancement for immunoelectron microscopy has not been available in bacteriology, the morphological localization of proteins of Helicobacter pylori is not well known. In this report, we established a method of contrast enhancement in immunoelectron microscopy in this organism. Immunostained ultrathin sections are stained with a mixture of alcian blue and osmium tetroxide prior to staining with uranyl acetate. This method of staining provided good contrast enhancement of the bacterial cell wall and membrane without any loss of immunolabeled gold particles on the ultrathin section.

Acrylic Resins↗