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K Imai

Publications and source records attributed to K Imai.

At least 37 records · Page 2Linked to original sources
PubMed2005

Gene expression profiling of colorectal adenomas and early invasive carcinomas by cDNA array analysis.

It is generally accepted that most colorectal carcinomas arise in pre-existing adenomas. Morphologically, colorectal adenomas can be divided into two groups, protruded type and flat type. The aim of this study was to clarify relevant alterations of gene expression associated with the early stage of colorectal carcinogenesis. Using cDNA array, we analysed the expression profiles of 550 cancer-related genes in 36 colorectal adenomas (18 flat-type and 18 protruded-type adenomas) and 14 early invasive carcinomas. Among the 550 genes, we chose 32 genes the average expression levels of which were at least three-fold up- or downregulated in tumour tissues compared with levels in matched normal tissues. A total of 13 and 19 genes were identified as up- and downregulated genes in tumour tissues, respectively. Among the upregulated genes, the average expression levels of E1AF, bone morphogenic protein (BMP)-4, insulin-like growth factor (IGF)-2, inducible nitric oxide synthase (iNOS), tissue inhibitors of metalloproteinase (TIMP)-1, Smad4, and nm23 in tumour tissues were over five times higher than those in matched normal tissues. Colorectal adenomas and early invasive carcinomas were divided into two major clusters by clustering analysis. Moreover, flat- and protruded-type adenomas were divided into two major clusters by clustering analysis. The expression profiles obtained by the cDNA array clearly indicate that colorectal adenomas and early invasive carcinomas have specific expression profiles. Likewise, the gene expression profiles of flat- and protruded-type adenomas are different. These results indicate that molecular classification of early colorectal tumours by a cDNA array is feasible.

Adenoma↗
PubMed2005

Aberrant DNA methylation associated with silencing BNIP3 gene expression in haematopoietic tumours.

Hypoxia is a key factor contributing to the progression of human neoplasias and to the development of resistance to chemotherapy. BNIP3 is a proapoptotic member of the Bcl-2 protein family involved in hypoxia-induced cell death. We evaluated the expression and methylation status of BNIP3 gene to better understand the role of epigenetic alteration of its expression in haematopoietic tumours. Methylation of the region around the BNIP3 transcription start site was detected in four acute lymphocytic leukaemia, one multiple myeloma and one Burkitt lymphoma cell lines, and was closely associated with silencing the gene. That expression of BNIP3 was restored by treatment with 5-aza2'-deoxycytidine (5-aza-dC), a methyltransferase inhibitor, which confirmed the gene to be epigenetically inactivated by methylation. Notably, re-expression of BNIP3 using 5-aza2-dC also restored hypoxia-mediated cell death in methylated cell lines. Acetylation of histone H3 in the 5' region of the gene, which was assessed using chromatin immunoprecipitation assays, correlated directly with gene expression and inversely with DNA methylation. Among primary tumours, methylation of BNIP3 was detected in five of 34 (15%) acute lymphocytic leukaemias, six of 35 (17%) acute myelogenous leukaemias and three of 14 (21%) multiple myelomas. These results suggest that aberrant DNA methylation of the 5' CpG island and histone deacetylation play key roles in silencing BNIP3 expression in haematopoietic tumours.

Base Sequence↗
PubMed2005

The cytoplasmic expression of E-cadherin and beta-catenin in bovine trophoblasts during binucleate cell differentiation.

Binucleate cells are endocrine cells generated by the acytokinesis and endoreduplication of the trophectoderm in the ruminant placenta. These cells are migratory and secrete hormones into the maternal circulation after fusing with uterine epithelial cells. In this study, we performed immunohistochemistry for E-cadherin and beta-catenin in bovine placenta and a bovine trophoblast cell line (BT-1). We found that E-cadherin and beta-catenin were distributed not only at the cell to cell boundary but throughout the cytoplasm in binucleate cells, although they were concentrated at the cell to cell boundary in epithelial cells in bovine placenta. Moreover, beta-catenin was detected in the nuclei of binucleate cells. Binucleate cells after fusion with uterine epithelial cells (feto-maternal hybrid cells) in the maternal side showed no intracellular expression of E-cadherin and beta-catenin. The transformation into binucleate cells in the BT-1 cell line was also accompanied by the cytoplasmic accumulation of E-cadherin and beta-catenin. We further demonstrated that levels of cytoplasmic beta-catenin were well correlated with the DNA content of binucleate cells in BT-1. The dynamic changes in the distribution of E-cadherin and beta-catenin suggest an important role in binucleate cells, including the rearrangement of cadherin-mediated cell adhesions during cell migration and the onset of endoreduplication probably via the nuclear transfer of beta-catenin.

Actins↗
PubMed2005

Open radiofrequency ablation for the management of intractable epilepsy associated with sessile hypothalamic hamartoma.

Sessile hypothalamic hamartoma (HH) often causes intractable epilepsy, which is difficult to control even by microsurgical resection and gamma knife surgery (GKS), especially when the hamartoma is intrahypothalamic, large, or irregularly shaped. We successfully applied radiofrequency ablation (RFA) to reduce its epileptogenicity and to disconnect seizure propagation. The patient was a 26-year-old man who presented with refractory epilepsy and severe mental retardation from age 6 months. He had undergone three surgeries yielding partial resection and conventional irradiation treatments. The residual HH was thin and shaped like a bent plate, attached widely to the floor of the third ventricle. He underwent open RFA via the transcallosal sub-choroidal approach under strict image guidance, which resulted in immediate and remarkable seizure remission without complications. This suggests that open RFA is a minimally invasive technique for an irregularly shaped HH that is difficult to treat by other modalities.

Adult↗
PubMed2005

Insulin-like growth factor I receptor blockade enhances chemotherapy and radiation responses and inhibits tumour growth in human gastric cancer xenografts.

BACKGROUND AND AIMS: Insulin-like growth factor (IGF) I receptor (IGF-Ir) signalling is required for carcinogenicity and proliferation of many tumours but this pathway has not been studied in detail in gastric cancer. We have previously shown successful therapy for colorectal, pancreatic, and lung cancer using recombinant adenoviruses expressing dominant negative (dn) IGF-Ir. In this study, we sought to better dissect the role of IGF-Ir on progression of gastric cancer and determine whether IGF-Ir targeted adenoviruses represent potentially effective therapeutics for human gastric cancer. METHODS: We assessed the effect of IGF-Ir ligands on proliferation and survival in gastric cancer cells in culture. Then, recombinant adenoviruses expressing truncated IGF-Ir (482 and 950 amino acids long, IGF-Ir/dn) that function as dn inhibitors were studied in the treatment of human gastric cancer xenografts. We characterised the effects of IGF-Ir/dn on signalling blockade, growth, apoptosis induction, and in vivo therapeutic efficacy. RESULTS: IGF-Ir signalling promoted tumour growth and survival in gastric cancer. IGF-Ir/dn expression suppressed tumorigenicity both in vitro and in vivo and upregulated stressor induced apoptosis. IGF-Ir/dn blocked Akt-1 activation induced by IGF-I, IGF-II, and des(1-3)IGF-I, but not by insulin. IGF-Ir/dn expression increased radiation and chemotherapy induced apoptosis and the combination of IGF-Ir/dn and chemotherapy was very effective against tumours in mice. In an intraperitoneal model, IGF-Ir/dn therapy also suppressed peritoneal dissemination. CONCLUSIONS: IGF-Ir is involved in the regulation of survival and cell growth in human gastric cancer and may be a good molecular therapeutic target. Adenovirus-IGF-Ir/dn may thus have therapeutic use in gastric cancer.

Adenoviridae↗
PubMed2005

Tumour matrilysin expression predicts metastatic potential of stage I (pT1) colon and rectal cancers.

BACKGROUND AND AIMS: Nodal metastases are indisputable determinants of prognosis for colon and rectal cancer. Using classical histological criteria, many attempts to predict nodal metastasis have failed, preventing the adequate management of stage I (pT1) cancer. We investigated the role of tumour matrilysin in predicting metastatic potential, and discuss its potential use in individualising treatment of pT1 colon and rectal cancer. METHODS: The gene signature associated with nodal metastasis was investigated by cDNA array in 24 colon and rectal cancers. We studied 494 colon and rectal cancer patients to identify risk factors for nodal metastasis and evaluated the potential to predict nodal metastasis by either the logistic regression model or the Bayesian neural network model with built-in matrilysin. We then inferred possible causality of nodal metastasis from structural equation modelling. RESULTS: cDNA array revealed that matrilysin was maximally upregulated in the metastasis signature identified. Tumour matrilysin expression emerged as a stage independent risk factor for nodal metastasis, resulting in a similar predictive performance in receiver operating characteristic curve analysis in the two models. A Bayesian approach called automatic relevance determination identified matrilysin as one of the most relevant predictors examined. Structural equation modelling suggested possible direct causality between matrilysin and nodal metastasis. CONCLUSIONS: We have provided evidence that tumour matrilysin expression is a promising biomarker predicting nodal metastasis of colon and rectal cancer. Analysis of tumour matrilysin expression would help clinicians achieve the goal of individualised cancer treatment based on the metastatic potential of pT1 colon and rectal cancer.

Adenocarcinoma↗
PubMed2005

MUC4 expression is a novel prognostic factor in patients with invasive ductal carcinoma of the pancreas.

BACKGROUND: Many patients with invasive ductal carcinoma of the pancreas (IDC) have a poor outcome. MUC4 expression has been implicated as a marker for diagnosis and progression of IDC, but there are no studies of the relation between MUC4 expression and patient prognosis in IDC. AIMS: To investigate the prognostic significance of MUC4 expression in IDC. METHODS: The expression profiles of MUC4, ErbB2, p27, and MUC1 were investigated in IDC tissues from 135 patients by means of immunohistochemistry. RESULTS: MUC4 was expressed in 43 of the 135 patients with IDC (31.9%). The survival of 21 patients with high MUC4 expression (>20% of neoplastic cells stained) was significantly worse than that of the 114 patients with low MUC4 expression (<20% of neoplastic cells stained) (p = 0.0043). Univariate analysis showed that high MUC4 expression (p = 0.0061), large primary tumour status (>T2) (p = 0.0436), distant metastasis (p = 0.0383), lymphatic invasion (p = 0.0243), and surgical margins (p = 0.0333) were significant risk factors affecting the outcome of patients with IDC. Backward stepwise multivariate analysis showed that MUC4 expression (p = 0.0121), lymph node metastasis (p = 0.0245), and lymphatic invasion (p = 0.0239) were significant independent risk factors. ErbB2, p27, and MUC1 were not independent risk factors. CONCLUSIONS: This study shows that MUC4 expression in IDC is a new independent factor for poor prognosis and predicts the outcome of patients with IDC.

Adult↗
PubMed2005

Correlation of lung surface area to apoptosis and proliferation in human emphysema.

Pulmonary emphysema is associated with alterations in matrix proteins and protease activity. These alterations may be linked to programmed cell death by apoptosis, potentially influencing lung architecture and lung function. To evaluate apoptosis in emphysema, lung tissue was analysed from 10 emphysema patients and six individuals without emphysema (normal). Morphological analysis revealed alveolar cells in emphysematous lungs with convoluted nuclei characteristic of apoptosis. DNA fragmentation was detected using terminal deoxynucleotide transferase-mediated dUTP nick-end labelling (TUNEL) and gel electrophoresis. TUNEL revealed higher apoptosis in emphysematous than normal lungs. Markers of apoptosis, including active caspase-3, proteolytic fragment of poly (ADP-ribose) polymerase, Bax and Bad, were detected in emphysematous lungs. Linear regression showed that apoptosis was inversely correlated with surface area. Emphysematous lungs demonstrated lower surface areas and increased cell proliferation. There was no correlation between apoptosis and proliferation, suggesting that, although both events increase during emphysema, they are not in equilibrium, potentially contributing to reduced lung surface area. In summary, cell-based mechanisms associated with emphysematous parenchymal damage include increased apoptosis and cell proliferation. Apoptosis correlated with airspace enlargement, supporting epidemiological evidence of the progressive nature of emphysema. These data extend the understanding of cell dynamics and structural changes within the lung during emphysema pathogenesis.

Adult↗
PubMed2005

[Infective endocarditis with splenic abscess and cerebral hemorrhage].

A 65-year-old man was admitted with ataxic gait and high fever. Brain magnetic resonance imaging (MRI) showed multiple cerebral hemorrhages and echocardiogram showed vegetations attached to the mitral valve and moderate mitral regurgitation. No microorganisms were identified by blood culture examination. Despite adequate treatment with antibiotics, large multiple splenic abscesses were detected by computed tomography (CT), the patient complained of fever and the value of CRP was increased again. We decided to first perform splenectomy, followed by mitral valve repair and maze operation. The pathology of the spleen showed findings consistent with large abscesses due to septic emboli. The postoperative course was uneventful.

Abscess↗
PubMed2004

Hypernuclear fine structure in (16)(Lambda)O and the LambdaN tensor interaction.

We have observed two gamma-ray transitions in (16)(Lambda)O from the 6.6 MeV excited 1(-)(2) state to both ground-state spin-doublet members (1(-)(1),0(-)) by the (K-,pi(-)gamma) reaction. We have obtained the ground-state doublet spacing to be 26.4+/-1.6(stat)+/-0.5(syst) keV and the excitation energy of the 1(-)(2) state to be 6561.7+/-1.1(stat)+/-1.7(syst) keV. The ground-state doublet spacing provides a small but nonzero strength of the tensor interaction between a Lambda and a nucleon. This is the first experimental result on the LambdaN tensor interaction.

Journal Article↗
PubMed2004

Clinical and pathological differences between Mikulicz's disease and Sjögren's syndrome.

OBJECTIVE: Mikulicz's disease (MD) has been included within the diagnosis of primary Sjögren's syndrome (SS), but represents a unique condition involving enlargement of the lachrymal and salivary glands and characterized by few autoimmune reactions and good responsiveness to glucocorticoids. We have previously described elevated immunoglobulin (Ig) G4 in the serum of four patients with MD. In this paper, we accumulated more MD cases and undertook clinical and histopathological analysis of these patients to clarify differences between MD and SS. METHODS: We diagnosed seven patients with MD according to the following criteria: (i) visual confirmation of symmetrical and persistent swelling in more than two lachrymal and major salivary glands; (ii) prominent mononuclear infiltration of lachrymal and salivary glands; and (iii) exclusion of other diseases that present with glandular swelling, such as sarcoidosis and lymphoproliferative disease. We summarized the clinical and serological characteristics (IgG subclasses and IFN-gamma/IL-4 ratio) of seven patients with MD, compared with SS with glandular swelling (SSw) and without glandular swelling (SSo). After steroid administration, we analysed changes in IgG subclasses in MD. Labial salivary gland specimens in MD, SSw and SSo were stained with anti-IgG4 antibodies. RESULTS: The concentration (+/-s.d.) of IgG4 was 1169.7 +/- 892.2 mg/dl in MD, 24.4 +/- 7.0 mg/dl in SSw (P<0.005) and 82.6 +/- 189.7 mg/dl in SSo (P<0.005). The IFN-gamma/IL-4 ratio was 0.392 +/- 0.083 (0.78 +/- 0.23/2.14 +/- 0.31 IU/pg) in MD, 0.004 +/- 0.002 (0.20 +/- 0.07/57.02 +/- 14.05 IU/pg) in SSw (P<0.05) and 0.012 +/- 0.009 (0.58 +/- 0.86/116.24 +/- 207.65 IU/pg) in SSo (P<0.05). The concentration (+/-s.d.) of IgG4 in MD decreased to 254.0 +/- 50.3 mg/dl (P<0.05) after glucocorticoid treatment. Histopathologically, only MD was associated with prominent infiltration of IgG4-positive plasmacytes into lachrymal and salivary glands. CONCLUSION: Mikulicz's disease is quite different from SS clinically and histopathologically. MD is suggested to be an IgG4-related systemic disease.

Aged↗
PubMed2004

A new diagnostic test for VLCAD deficiency using immunohistochemistry.

BACKGROUND: Muscle pathology is often unhelpful in elucidating the specific underlying abnormality in patients with metabolic myopathy with rhabdomyolysis, including very-long chain acyl-CoA dehydrogenase (VLCAD) deficiency. Biochemical analyses require large amounts of biopsy samples for each enzyme assay. OBJECTIVE: To develop a more efficient diagnostic method for VLCAD deficiency. METHODS: The authors performed immunohistochemical analysis using an antibody to VLCAD on muscles from 344 patients (226 men and 118 women) without a specific diagnosis who had at least one of the following symptoms: myoglobinuria, high CK level, muscle pain, muscle stiffness, sudden infant death syndrome, and Reye-like syndrome. RESULTS: Immunoreactivity to VLCAD was absent or markedly reduced in 13 patients. Biochemical analyses confirmed that all these patients had low enzymatic activity and reduced amount of protein. They all had the myopathic phenotype. The authors identified homozygous or compound heterozygous mutations in all of them. All recombinant proteins had reduced enzymatic activity except for 128G>A (G43D) and 796C>G (P266A) mutants, indicating that they are neutral polymorphisms. CONCLUSIONS: The new screening method for the detection of VLCAD deficiency using an immunohistochemical technique identified 13 new Japanese patients with VLCAD deficiency.

Acyl-CoA Dehydrogenase, Long-Chain↗
PubMed2004

Inactivation of class II transactivator by DNA methylation and histone deacetylation associated with absence of HLA-DR induction by interferon-gamma in haematopoietic tumour cells.

By presenting immunogenic peptides at the cell surface, major histocompatibility complex (MHC) class II molecules play a key role in the control of adaptive immune responses. Whether expressed constitutively or induced by interferon-gamma, expression of MHC class II molecules is regulated via coactivator class II transactivator (CIITA); moreover, suppression of their expression is one mechanism by which cancer cells escape host immunity. In this study, we surveyed the relationship between the expression of one MHC class II antigen, HLA-DR, and its coactivators in a group of haematopoietic cell lines, and explored the role of the aberrant DNA methylation in silencing HLA-DR expression. Among 26 cell lines studied, HLA-DR expression was lost from eight T-cell and two myeloid leukaemia cell lines, and this loss was closely associated with suppression of CIITA-PIV expression. Notably, nine of the 10 cell lines that lost CIITA-PIV expression showed methylation of the gene's 5' CpG island. Thus, DNA methylation is believed to inhibit the expression of MHC class II molecules in haematopoietic tumour cells by silencing its coactivator, CIITA-PIV. Furthermore, methylation of CIITA-PIV was detected in seven of 32 primary acute myeloid leukaemia specimens, indicating that epigenetic alteration is not a cell line-specific phenomenon. Collectively, these data suggest that, by suppressing expression of MHC class II molecules, epigenetic inactivation of CIITA provides a survival advantage to a subset of haematopoietic tumours.

Acetylation↗
PubMed2004

Temporospatial expression of placental lactogen and prolactin-related protein-1 genes in the bovine placenta and uterus during pregnancy.

The anatomical location of binucleate cells (BNC) influences protein expression but not steroid synthesis in ruminants. In order to determine if BNC in disparate locations differentially express bovine placental lactogen (bPL) and prolactin-related protein-1 (bPRP-1), we quantitated bPL and bPRP-1 transcripts in placentomal (cotyledonary, caruncular) and interplacentomal (intercotyledonary, intercaruncular) tissues throughout pregnancy in the bovine using real-time reverse transcription PCR (RT-PCR) and in situ hybridization. Levels of both bPL and bPRP-1 transcripts at peri-implantation were significantly higher (P < 0.01) in the fetal membrane than in caruncular and intercaruncular tissues. Thereafter, mRNA for these related proteins demonstrated different spatial as well as temporal patterns of expression. Levels of bPRP-1 transcripts peaked at day 60 of pregnancy. Between day 60 and 100, bPRP-1 transcripts fell by approximately sevenfold (P < 0.01) in cotyledonary and intercotyledonary tissues, and fourfold in caruncular (P < 0.01) tissue. Levels of bPRP-1 transcripts remained low in the cotyledonary, intercotyledonary, and caruncular tissues until peripartum. In contrast, bPL expression in placentomes increased with progression of gestation (P < 0.01), but decreased in interplacentomal tissue around peripartum. To conclude, disparate patterns of bPRP-1 and bPL genes are transcribed in the placentomal and interplacentomal tissues during gestation in the bovine, suggesting that these prolactin-like hormones serve distinct functions and are regulated differently in the uteroplacental unit in this species.

Animals↗