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Y Kato

Publications and source records attributed to Y Kato.

At least 145 records · Page 8Linked to original sources
PubMed2001

Relationships between the activities in vitro and in vivo of various kinds of ribozyme and their intracellular localization in mammalian cells.

Nineteen different functional RNAs were synthesized for an investigation of the actions of ribozymes, in vitro and in vivo, under the control of two different promoters, tRNA or U6, which localize transcripts either in the cytoplasm or in the nucleus. No relationships were found between the activities of these RNAs in cultured cells and the kinetic parameters of their respective chemical cleavage reactions in vitro, indicating that in no case was chemical cleavage the rate-limiting step in vivo. For example, a hepatitis delta virus (HDV) ribozyme, whose activity in vitro was almost 3 orders of magnitude lower than that of a hammerhead ribozyme, still exhibited similar activity in cells when an appropriate expression system was used. As expected, external guide sequences, the actions of which depend on nuclear RNase P, were more active in the nucleus. Analysis of data obtained with cultured cells clearly demonstrated that the cytoplasmic ribozymes were significantly more active than the nuclear ribozymes, suggesting that mature mRNAs in the cytoplasm might be more accessible to antisense molecules than are pre-mRNAs in the nucleus. Our findings should be useful for the future design of intracellularly active functional molecules.

Base Sequence↗
PubMed2001

Geranylgeranylacetone induces antiviral gene expression in human hepatoma cells.

Geranylgeranylacetone (GGA), an isoprenoid compound, is used clinically as an anti-ulcer drug. Since some isoprenoids including retinoids have anti-tumor and anti-viral activities in a variety of cell types, we investigated whether GGA could induce anti-viral proteins in human hepatoma cells. The HuH-7 and HepG2 cells were treated with GGA, and expression of anti-viral proteins such as 2'5'-oligoadenylate synthetase (2'5'-OAS) and double-stranded RNA-dependent protein kinase (PKR) in these cells was analyzed. GGA stimulated 2'5'-OAS and PKR gene expression at the transcriptional level through the formation of interferon-stimulated gene factor 3 (ISGF3), which regulates both gene transcription. By Western blotting, GGA induced expression of signal transducers and activators of transcription 1, 2 (STAT1, STAT2) and p48 proteins, components of ISGF3, together with the phosphorylation of STAT1. These results suggest that GGA acts as a potent inducer of anti-viral gene expression by stimulating the ISGF3 formation in human hepatoma cells.

2',5'-Oligoadenylate Synthetase↗
PubMed2001

Molecular cloning and characterization of DEC2, a new member of basic helix-loop-helix proteins.

DEC1 is a basic helix-loop-helix (bHLH) protein related to Drosophila Hairy, Enhancer of split and HES, and involved in the control of proliferation and/or differentiation of chondrocytes, neurons, etc. We report here the identification and characterization of human, mouse and rat DEC2, a novel member of the DEC subfamily. DEC2 had high (97%) and moderate (52%) similarities in the bHLH region and the Orange domain with DEC1, respectively. However, DEC2, but not DEC1, had alanine and glycine-rich regions in the C-terminal half. Unlike Hairy, Enhancer of split and HES, DEC2 lacked the WRPW motif for interaction with the corepressor Groucho. The DEC2 gene was mapped to human chromosome 12p11.23-p12.1, mouse chromosome 6 G2-G3 and rat chromosome 4q43 distal-q4, where the conserved linkage homology has been identified among these species. Unlike DEC1, which was broadly expressed in many tissues, DEC2 showed a more restricted pattern of mRNA expression. The DEC subfamily proteins may play an important role in tissue development.

Amino Acid Sequence↗
PubMed2001

Infiltration of cervical lymph nodes by B- and T-cell non-Hodgkin's lymphoma and Hodgkin's lymphoma: preliminary ultrasonic findings.

Ultrasonography has been used in the evaluation of enlarged lymph nodes in patients with malignant lymphoma, which comprises a variety of histopathological subtypes. We assessed ultrasonic findings of infiltration in cervical lymph nodes of 47 patients with previously untreated malignant lymphoma and correlated them with histopathological subtypes. Common findings among various histopathological subtypes were hypoechoic masses, spot and/or line echoes, involvement of multiple nodes, and posterior enhancement. In addition, each histopathological subtype showed characteristic findings: Hodgkin's disease had a contour with a lobular pattern (9/10 cases), septum-like echo (9/10 cases), and tubular structure (9/10 cases) in the internal echo, reflecting histopathologically fibrous connective tissue surrounding lymph nodes and small vessels. In B-cell lymphoma, there was characteristically a tendency for lymph node fusion (19/28 cases) and spot and/or line echoes (17/28 cases), reflecting histopathological replacement and destruction of the structure of lymph node and capsule by proliferation of lymphocytes. These findings were strengthened in diffuse large B-cell lymphoma. T-cell lymphoma was distinguished from other types of lymphoma by the presence of a hilum-like echo (6/9 cases), reflecting histopathologically prominent vascularization in lymph nodes accompanied by a dilated hilum area. In summary, this preliminary study suggests that ultrasonic findings of infiltration of cervical lymph nodes in major subtypes of malignant lymphoma could reflect characteristic histopathological structures, therefore providing information helpful for differentiating them.

Adult↗
PubMed2001

Investigation of 5-FU disposition after oral administration of capecitabine, a triple-prodrug of 5-FU, using a physiologically based pharmacokinetic model in a human cancer xenograft model: comparison of the simulated 5-FU exposures in the tumour tissue between human and xenograft model.

The nonlinear pharmacokinetics of capecitabine, a triple prodrug of 5-FU preferentially activated in tumour tissues, was investigated in human cancer xenograft models. A physiologically based pharmacokinetic (PBPK) model integrating the activation process of capecitabine to 5-FU and 5-FU elimination was constructed to describe the concentration/time profiles of capecitabine and its three metabolites, including 5-FU, in blood and organs. All the biochemical parameters (enzyme kinetic parameters, plasma protein binding and tissue binding of capecitabine and its metabolites) integrated in this model were measured in vitro. The simulated curves for the blood and tumour concentrations of capecitabine and its metabolites can basically describe the observed values. A simple prodrug of 5-FU, doxifluridine, is known to be activated to 5-FU to some extent in the gastrointestinal (GI) tract, causing diarrhoea, which is the dose limiting side effect of doxifluridine. Consequently, the therapeutic index (the ratio of 5-FU AUC in the tumour to that in GI) after the administration of effective dose capecitabine was predicted by this PBPK model and found to be five times and 3000 times greater than that of doxifluridine and 5-FU, respectively. This was compatible with the previous result for the difference in the ratio of the toxic dose to the minimum effective dose between capecitabine and doxifluridine, suggesting that 5-FU preferentially accumulates in tumour tissue after oral administration of capecitabine compared with the other drugs (doxifluridine and 5-FU). The 5-FU AUC in tumour tissue of human cancer xenograft models at the minimum effective dose was comparable with those estimated for humans at the clinical dose. In addition, the predicted therapeutic indices at the respective doses were correlated well between humans and mice (xenograft model). These results suggest that the 5-FU AUC in human tumour tissue at its clinically effective dose can be predicted based on the PBPK model inasmuch as the 5-FU AUC in a human cancer xenograft model at its effective dose may be measured or simulated.

Administration, Oral↗
PubMed2001

Cytostatic effect of inostamycin, an inhibitor of cytidine 5'-diphosphate 1,2-diacyl-sn-glycerol (CDP-DG): inositol transferase, on oral squamous cell carcinoma cell lines.

Inostamycin, which was recently isolated from Streptomyces sp. MH816-AF15 as an inhibitor of cytidine 5'-diphosphate 1,2-diacyl-sn-glycerol (CDP-DG): inositol transferase, caused a G1-phase accumulation in the cell cycle of small cell lung carcinomas. To investigate whether the cytostatic effect of inostamycin is restricted to lung carcinoma cell lines or applicable to other type of cells, we tested five oral squamous cell carcinoma (SCC) cell lines. Cell growth was suppressed in 62.5--125 ng/ml inostamycin in the culture medium in all oral cancer cell lines tested, with non-viable cells being <1%, indicating inostamycin is cytostatic on SCC cell lines. Decrease in cyclin D1 mRNA and protein expression due to the inostamycin treatment was accompanied by suppression of phosphorylated retinoblastoma susceptibility gene product (pRB-P) levels. Moreover, flow cytometric analysis showed that inostamycin induced an increase in G1/G0 cells (1.2--3.2 fold) over 24 h. These results suggest that inostamycin is a useful agent for tumour dormant cytostatic therapy for oral SCC.

Antineoplastic Agents↗
PubMed2001

Production of experimental autoimmune sialadenitis in mice immunized with homologous salivary gland extract and Klebsiella O3 lipopolysaccharide.

An experimental murine model for autoimmune sialadenitis was produced by repeated immunization of homologous salivary gland extract together with Klebsiella O3 lipopolysaccharides as an immunological adjuvant. The cell infiltration was observed in the salivary glands of mice immunized more than twice. Inflammatory cells consisting mainly of CD4+ T cells and CD8+ T cells accumulated at the perivascular regions. There was hyperplasia and enlargement of ductal epithelial cells in the secretory acinar units in salivary glands of repeatedly immunized mice. The repeated immunization developed delayed-type hypersensitivity and autoantibody production to the homologous salivary gland extract. The immunohistochemical analysis showed positive staining on the cuboidal cells in the intercalated ducts, and the columnar pseudostratified cells in the striated ducts. Organ-specific antigens with molecular weights ranging from 20 to 90 kDa were recognized by the sera from immunized mice. Therefore, it was suggested that the sialadenitis was produced by the autoimmune mechanism and might be a new experimental model for characterization of the pathogenesis of autoimmune sialadenitis.

Adjuvants, Immunologic↗
PubMed2001

Intralobular heterogeneity of oxidative stress and cell death in ischemia-reperfused rat liver.

The relationship between zonal oxidative stress and cell death after ischemia-reperfusion injury in rat liver was investigated. Oxidative stress was detected in situ by perfusion with nitroblue tetrazolium, which is converted to insoluble blue formazan by reducting agents. Cell death was detected in situ by perfusion with trypan blue. When isolated liver was perfused after 30 or 60 min of warm ischemia, oxidative stress was detected in periportal parenchymal cells after 30 min of reperfusion. It spread in the shape of a doughnut to midzonal cells after 60 min of reperfusion. On the other hand, cell death was observed in parenchymal cells that were within the doughnut-like area in which oxidative stress was detected. The extent of oxidative stress and cell death was higher after 60 min of ischemia than after 30 min of ischemia. In nonparenchymal cells, oxidative stress was observed in midzonal and pericentral regions after only 12 min of reperfusion, but minor cell death was observed only in periportal and midzonal regions after 30 min of reperfusion. Administration of allopurinol, an inhibitor of xanthine oxidase, suppressed oxidative stress and cell death in periportal parenchymal cells. These findings indicate that periportal and midzonal parenchymal cell death can be caused by zone-specific and xanthine-oxidase-mediated oxidative stress in parenchymal cells.

Allopurinol↗
PubMed2001

Secondary mitral valve replacement in antiphospholipid syndrome and chronic renal failure.

A 48-year-old woman admitted with progressive dyspnea had previously been diagnosed with systemic lupus erythematosus, antiphospholipid syndrome, and chronic renal failure, and had undergone mitral valve replacement with a Carpentier-Edwards pericardial bioprosthesis for mitral insufficiency 9 years before. She suffered a cerebral infarction 5 years earlier, despite appropriate anticoagulant therapy. On admission, echocardiography showed severe bioprosthetic stenosis. Repeat mitral valve replacement was conducted using a Mosaic bioprosthesis. On postoperative day 2, when heparinization was commenced, she suddenly had an epileptic fit. She also developed ischemic necrosis of the fingers and toes, considered secondary to microthrombosis. Aspirin was administered and heparin replaced by warfarin sodium. Necrosis gradually disappeared, and she was discharged 3 months after surgery. The original bioprosthesis showed degenerative changes with significant thrombus formation on cusps, thought to be mainly due to her hypercoagulable state. Considering the thrombophilic tendency in patients with antiphospholipid syndrome, strict management of anticoagulant therapy is required.

Adult↗
PubMed2001

Early and late outcomes after reoperation for prosthetic valve endocarditis.

OBJECTIVE: Prosthetic valve endocarditis remains a challenging complication after heart valve replacement. To identify predictive risk factors, we have reviewed 30 patients who underwent surgery for prosthetic valve endocarditis between March 1986 and May 1999. METHODS: There were 15 men and 15 women (mean age 51 years). Prosthetic valve endocarditis was classified as early (< or = 1 year after operation) in 10 cases, and as late in the other 20 cases. The most common indication for surgery was moderate to severe congestive heart failure due to prosthetic valve dysfunction in 21 (70%) patients. The average follow-up period was 6.5 years, with a range of 0.3 to 14.1 years. RESULTS: The most common microorganism was Staphylococcus epidermidis in both patients with early (50%) and late prosthetic valve endocarditis (25%). The in-hospital mortality was 13.3% (4/30). There were six late deaths. The actuarial survival at 5 years was 78% and 66% at 10 years. An early onset of prosthetic valve endocarditis was the only significant determinant of both in-hospital mortality (p = 0.005) and overall mortality (p = 0.021). Emergency surgery had a statistically significant relationship with in-hospital mortality (p = 0.045). No significant influence on mortality after reoperation for prosthetic valve endocarditis was found in age, sex, valve position, antecedent native valve endocarditis, or in the type of pathological findings (ring abscess, valve dehiscence, and vegetation). CONCLUSION: Early onset of prosthetic valve endocarditis and emergency surgery were important risk factors for mortality due to prosthetic valve endocarditis.

Adult↗
PubMed2001

Mitral insufficiency associated with primary antiphospholipid syndrome and chronic renal failure.

We report a case of 52-year-old woman with primary antiphospholipid syndrome who developed mitral insufficiency and chronic renal failure. Continuous ambulatory peritoneal dialysis was started preoperatively due to thrombocytopenia that was aggravated by hemodialysis. Mitral annuloplasty was performed since the mitral valve was not severely damaged. Her postoperative hemodynamics were stable, and anticoagulant therapy was controlled easily. She recovered from severe thrombocytopenia while on continuous ambulatory peritoneal dialysis. Valvular heart disease is a well known feature of primary antiphospholipid syndrome, and there have been several reports about valve replacement in patients who had antiphospholipid syndrome with or without systemic lupus erythematosus. However, valve repair has been reported in only a few such patients. We believe that valve repair is better than valve replacement in patients with antiphospholipid syndrome because of its hypercoagulable tendency. In addition, it seems that continuous ambulatory peritoneal dialysis is a suitable method for the perioperative management of patients with antiphospholipid syndrome who suffer from chronic renal failure as well as thrombocytopenia, and require cardiac surgery under cardiopulmonary bypass.

Antiphospholipid Syndrome↗
PubMed2001

Bilateral transient radial nerve palsies in an infant after cardiac surgery.

PURPOSE: To describe the case of an infant who suffered bilateral transient radial nerve palsies after cardiac surgery. CLINICAL FEATURES: A one-month-old baby was found to have bilateral wrist and finger drop after the removal of splints that has been applied to the right hand for 14 days and to the right hand for six days during perioperative management of Blalock-Taussig shunt surgery. The hand splints had been applied to the forearms with adhesive silky tape to keep peripheral vascular lines in place. The patient also suffered from several episodes of cardiogenic shock, hypoxemia and generalized edema relating to cardiac dysfunction during this fine period. Given the findings of no impairment of median or ulnar nerves and brachioradial muscle, it was suspected that bandaging with adhesive tapes caused peripheral radial nerve damage at the level of posterior interosseus nerve on forearm. Diminished oxygen delivery and edema may additionally have contributed to peripheral nerve ischemia. The aforementioned neurologic symptoms resolved spontaneously after several days. CONCLUSION: Prolonged compression by bandaging of splints on forearm may have resulted in ischemic damage to the posterior interosseus nerve branch combined with extensor carpi radialis longus nerve branch of the radial nerve. We should attempt to reduce the frequency and duration of splinting of the extremities, especially in sedated, paralyzed babies, given the potential risk of compression neuropathy.

Arteriovenous Shunt, Surgical↗
PubMed2001

Molecular cloning of the complement (C1r/C1s/MASP2-like serine proteases from the common carp (Cyprinus carpio).

The classical pathway of complement composed of C1, C4, and C2 is an antibody-dependent activation cascade that is present in jawed vertebrates. C1 is a Ca2+-dependent complex of C1q, C1r, and C1s, and analogous to an initiation complex of the lectin pathway of complement, which consists of the mannose-binding lectin (MBL) homologous to C1q and the MBL-associated serine proteases (MASPs) homologous to C1r and C1s. Thus divergence of Clq and MBL and that of C1r, C1s and the MASPs are considered to be crucial events in the establishment and evolution of the classical complement pathway. However, molecular information on the C1 subcomponents is very limited in lower vertebrates. Here we describe two distinct C1r/C1s/MASP2-like cDNA clones (C1r/s-A, C1r/s-B) isolated from the common carp (Cyprinus carpio). They share 83% identity at the amino acid level and have a domain structure similar to that of C1r/C1s/MASPs from other species. The serine protease domain of the carp homologues lacks the histidine loop and is encoded by a single exon containing an AGY codon for the active serine residue, as in mammalian C1r, C1s, and MASP2. Southern blot and PCR analyses indicated that the carp has at least three copies of the C1r/s-A gene and a single C1r/s-B gene. Although phylogenetic tree analysis does not definitively assign carp C1r/s-A and C1r/s-B, they might represent ancestral molecules which later diverged into C1r, C1s, and MASP2 of higher vertebrates.

Alleles↗
PubMed2001

Review of histological classifications of gastrointestinal epithelial neoplasia: differences in diagnosis of early carcinomas between Japanese and Western pathologists.

Gastrointestinal lesions considered to be high-grade adenoma/dysplasia by Western pathologists using the conventional Western classification are often diagnosed as carcinoma by Japanese pathologists using the Japanese group classification. To overcome these differences, the Padova classification, the Vienna classification, and a revision of the Vienna classification have recently been proposed. The clinical usefulness of these five classifications needs to be reviewed for early gastric, esophageal, and colorectal neoplasias. In 1998, 31 pathologists from 12 countries individually diagnosed the same 35 gastric, 21 esophageal, and 20 colorectal specimens. Their histological diagnoses can be classified conventionally and according to the newly proposed terminology, and from these data, the extent of agreement between pathologists with Western and Japanese viewpoints can be calculated, using kappa statistics. With the conventional Western, Japanese, Padova, Vienna, and revised classifications, the agreement scores were 37%, 37%, 71%, 71%, and 80%, respectively, for gastric lesions; 14%, 14%, 57%, 62%, and 67% for esophageal lesions; and 45%, 50%, 65%, 65%, and 70% for colorectal lesions. The kappa values were lower than 0.3 with the conventional Western and Japanese classifications, but higher than 0.5 for gastric lesions, higher than 0.3 for esophageal lesions, and higher than 0.4 for colorectal lesions with the newly proposed classifications. When the literature regarding treatment indications for early neoplastic lesions is reviewed, it becomes apparent that the categories of the revised classification would fit best with current clinical treatment considerations. This classification would be particularly useful for endoscopically resected specimens, to determine whether additional surgery with lymph node dissection is required. In conclusion, the use of the newly proposed terminology can, in large part, resolve the intercountry differences in the diagnosis of adenoma/dysplasia and early carcinoma. However, the newly proposed classifications should be used with caution for biopsy specimens, as sampling error may result in an underestimation of the neoplastic grade or depth of invasion. For the choice between endoscopic and surgical treatment, assessment of the depth of invasion by endoscopic inspection and ultrasound or radiography is essential.

Adenoma↗
PubMed2001

The effects of pedicle screw adjustments on the anatomical reduction of thoracolumbar burst fractures.

The short segmental pedicle screw device is widely used for the decompression of neural elements and reduction of normal anatomy. Many biomechanical studies concerning proper decompression are available. However, no study has determined the optimal device adjustment for reduction of the burst fracture to the normal anatomy. In this study, cadaveric thoracolumbar spine specimens (T11-L3) with L1 burst fractures were studied. A pedicle screw device was attached to the pedicles of the T12 and L2 vertebrae. Spinal postural changes were determined due to a set of eight clinically relevant adjustments of the device. The adjustments were combinations of axial translation (distraction/compression) and extension. The adjustments caused varying changes in spinal posture. The sequence of applying the translation and extension had no effect on the spinal posture changes. The adjustment combining 5 mm distraction with 6 degrees extension brought the burst fracture closest to the intact state, compared to all other adjustments. With this adjustment, on average the spine became 0.9 mm compressed and 2.0 degrees lordotic, compared to the intact. The results of the study show that the device adjustments of axial translation and sagittal angulation can be applied in any sequence, with the same results. The combination of 5 mm distraction with 6 degrees extension was the device adjustment that produced the closest anatomical reduction.

Adult↗
PubMed2001

The value of ultrasound-guided fine-needle aspiration cytology for thyroid nodules: an assessment of its diagnostic potential and pitfalls.

This study was conducted to assess the diagnostic potential and pitfalls of performing fine-needle aspiration cytology (FNAC) for thyroid nodules. We retrospectively analyzed 1,012 aspirated samples obtained from 806 thyroid nodules by the ultrasound (US)-guided method. Of these 806 nodules, 226 (31%) had been surgically treated, 152 (67%) of which were histologically diagnosed as malignant. The rate of sufficient aspirate was 82%, being lower in nodules with a diameter of less than 5mm (73%, P = 0.10); either calcified (77%, P = 0.043) or benign (72%, P = 0.0002). The accuracy of FNAC was 75%, the rate of indeterminate diagnosis was 16%, the false negative rate was 13%, and the positive malignancy rate was 99%. The rate of indeterminate diagnosis was higher in adenomatous goiter, follicular carcinoma, and malignant lymphoma, at P = 0.015, P = 0.0008, and P = 0.035, respectively. The accuracy was lower in follicular carcinoma and malignant lymphoma (both at P = 0.013). Sufficient aspirate was finally obtained from 701 (87%) of the 806 nodules by repeated aspiration. Of 152 malignant nodules, 28 (18%) were diagnosed after two or more aspirations, and the accuracy was improved to 81% by repeating the procedure. These findings indicated that repeated aspiration may be a simple and effective method of improving the diagnostic potential of FNAC.

Adenocarcinoma, Follicular↗