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Biomedical subjects

M Tada

Publications and source records attributed to M Tada.

At least 19 recordsLinked to original sources
PubMed2006

Absence of PIK3CA hotspot mutations in hepatocellular carcinoma in Japanese patients.

A recent study revealed that the p110alpha (PIK3CA), catalytic subunit of phosphatidylinositol 3-kinase (PI3K), is somatically mutated in many types of cancer. For example, PIK3CA is mutated in an estimated 35.6% of hepatocellular carcinoma (HCC) cases. To measure the frequency of PIK3CA hotspot mutations in Japanese HCC patients, exons 9 and 20 of the PIK3CA gene were sequenced in 47 clinical HCC samples. Contrary to expectations, no hotspot mutations were found any of the HCC samples. In addition, we found abnormally migrating waves near the end of exon 9 in the PCR chromatograms from 13 of the 47 samples. PCR amplification and subsequent cloning and sequencing revealed that these chromatograms contained two distinct sequences, the wild-type p110alpha sequence and a different sequence found on human chromosome 22q11.2, the Cat Eye Syndrome region, which contains a putative pseudogene of PIK3CA. These abnormally migrating waves were also found in noncancerous liver tissue, indicating that this was not a result of HCC-associated mutations. Therefore, it is likely that the percentage of hotspot mutations in the PIK3CA gene of Japanese HCC patients is lower than was previously reported.

Adult↗
PubMed2006

High-rate pulmonary involvement in autoimmune pancreatitis.

Autoimmune pancreatitis (AIP) has extrapancreatic complications such as Sjögren's syndrome, retroperitoneal fibrosis and sclerosing cholangitis. We studied 30 patients with AIP. Of these, we identified pulmonary involvement in four patients during follow up. Among them, two patients had respiratory failure. They showed good response to steroid therapy, but a higher dose of prednisolone was necessary to maintain remission than that required in biliary involvement. Elevation of immunoglobulin G(4) and Krebs von den Lungen-6 levels were characteristic of pulmonary involvement. They may be useful for early detection of pulmonary complication.

Aged↗
PubMed2005

Thirteen-week feeding study of thaumatin (a natural proteinaceous sweetener), sterilized by electron beam irradiation, in Sprague-Dawley rats.

This study was designed to evaluate and characterize any subchronic toxicity of thaumatin sterilized by electron beam irradiation (5.0 kGy) when administered at dietary levels of 0% (control), 0.3%, 1.0% and 3.0% to groups of 10 male and 10 female Crj: CD (SD) IGS rats for 13 weeks. Separate groups of both sexes received 3.0% non-irradiated thaumatin. There were no treatment-related clinical signs or adverse effects on the survival rate, body weight, food consumption, water consumption and urinalysis, ophthalmology, haematology, or blood biochemistry data. No treatment-related alterations in gross pathology or organ weights were found in any group. On histopathological examination, sporadic spontaneous lesions known to occur in this strain of rats were the only findings, with no specific relation to the test substance. Thus, the no-observed-adverse-effect-level (NOAEL) was judged to be a dietary level of at least 3.0% (2502 mg/kg body weight/day for males, 2889 mg/kg body weight/day for females) for electron beam irradiated thaumatin under the present experimental conditions. It was concluded that electron beam-irradiation of thaumatin does not cause changes of any toxicological significance.

Administration, Oral↗
PubMed2005

Extrahepatic biliary obstruction after percutaneous tumour ablation for hepatocellular carcinoma: aetiology and successful treatment with endoscopic papillary balloon dilatation.

BACKGROUND AND AIMS: Percutaneous tumour ablation (PTA), such as ethanol injection and radiofrequency ablation, is now recognised as a primary treatment for hepatocellular carcinoma (HCC). Although PTA is a relatively safe procedure, it can cause biliary obstruction as a rare complication. As patients with cirrhosis undergoing surgery or endoscopic retrograde cholangiopancreatography/sphincterotomy have a high mortality rate from bleeding, we adopted the use of endoscopic papillary balloon dilatation (EPBD) in these patients and now report the results. We retrospectively analysed the incidence of biliary obstruction after PTA and the efficacy of treatment with EPBD. PATIENTS AND METHODS: A total of 1043 patients with HCC were treated by PTA, of whom 538 were treated with transarterial embolisation with up to eight years of follow up. RESULTS: There were 17 (1.6%) cases of hilar obstruction due to tumour progression and 35 (3.4%) cases of extrahepatic obstruction. Apart from the expected causes of biliary obstruction (haemobilia n = 11, gallstones n = 11, and three miscellaneous causes), we found that 10 patients had obstruction due to biliary casts. This is the first description of biliary casts after percutaneous tumour ablation therapy. Extrahepatic biliary obstruction by procedure related haemobilia occurred within three days of PTA while other causes occurred between 0 and 17 (average 4.9) months. Biliary casts occurred more frequently after ethanol injection than after radiofrequency ablation. EPBD successfully dissipated biliary obstruction in 33 of 35 cases, while two died due to hepatic failure despite successful drainage. CONCLUSIONS: Extrahepatic biliary obstruction is an uncommon complication after PTA for HCC, and can be safely and effectively treated with EPBD, despite impaired liver function.

Adult↗
PubMed2004

Chelating of titanium by lactic acid in the water-soluble diammonium tris(2-hydroxypropionato)titanate(IV).

Stable water-soluble diammonium tris(2-hydroxypropionato)titanate(IV) [ammonium trilactatotitanate(IV)], (NH4)2[Ti(C3H4O3)3], was prepared in the crystalline form. According to the X-ray single-crystal diffraction data, this compound crystallizes in the cubic cell with a = 11.649(4) angstroms, space group P2(1)3 (no. 198), and has Z = 4 molecules per unit cell. The 13C NMR data and Raman and IR spectra support the determined structure. The absence of nonbonded functional groups restricts the formation of oligomers in contrast to the reported speciation of citratoperoxotitanate(IV) complexes.

Chelating Agents↗
PubMed2004

A prospective randomised study of "covered" versus "uncovered" diamond stents for the management of distal malignant biliary obstruction.

BACKGROUND AND AIM: Covered self-expandable metal stents (EMS) were recently developed to overcome tumour ingrowth in conventional EMS. However, supporting evidence for the efficacy of covered EMS is lacking. PATIENTS AND METHODS: We enrolled 112 patients with unresectable distal biliary malignancies. They were randomly assigned to polyurethane covered (n = 57) or original diamond stent (n = 55). RESULTS: Stent occlusion occurred in eight patients (14%) after a mean of 304 days in the covered group, and in 21 patients (38%) after a mean of 166 days in the uncovered group. The incidence of covered EMS occlusion was significantly lower than that of uncovered EMS (p = 0.0032). The cumulative stent patency of covered stents was significantly higher than that of uncovered stents (p = 0.0066). No tumour ingrowth occurred in the covered group while it was observed in 15 patients in the uncovered group. In subgroup analysis, the cumulative patency of the covered EMS was significantly higher in pancreatic cancer (p = 0.0363) and metastatic lymph nodes (p = 0.0354). There was no significant difference in survival between the two groups. Acute cholecystitis was observed in two of the covered group and in none of the uncovered group. Mild pancreatitis occurred in five of the covered group and in one of the uncovered group. CONCLUSIONS: Covered diamond stents successfully prevented tumour ingrowth and were significantly superior to uncovered stents for the treatment of patients with distal malignant biliary obstruction. However, careful attention must be paid to complications specific to covered self-expandable metal stents, such as acute cholecystitis and pancreatitis.

Acute Disease↗
PubMed2004

Radiation-heat synergism for inactivation of Alicyclobacillus acidoterrestris spores in citrus juice.

The objective of this study was to investigate the influence of electron-beam and gamma-ray irradiation and temperature (85 to 95 degrees C) on Alicyclobacillus acidoterrestris GD3B strain (NCIMB 13137) spores by calculating and comparing the decimal reduction dose or time (D-values). The survival rate of A. acidoterrestris spores decreased exponentially with irradiation doses of an electron beam or gamma ray. D-values determined for electron-beam and gamma-ray irradiated spores on filter paper ranged from 1.02 to 1.10 kGy. On the other hand, the thermal sterilization effect showed a single exponential decrease within 1.5-log decreases in cell numbers (D85 degrees C = 70.5 min, D90 degrees C = 16.1 min, and D95 degrees C = 5.19 min and z-value [change in temperature required to change the D-value] was 8.83 degrees C), and prolonged heating produced an increase of 10 to 13 times that of the thermal resistance. However, within all time ranges studied (5 to 360 min), a linear decrease in the D-value was observed with an increase in the temperature. A combination of two different methods, irradiation before heating, was appropriate for reducing the duration of the heat treatment required to achieve the inactivation of conidia. Moreover, a necessary radiation dosage for complete inactivation of A. acidoterrestris spores that contaminated dextrin was examined. Dextrin is often used in the juice industry as an augmentor, and it is known to be sometimes contaminated by these spores. The D-values of the spores in dextrin for electron-beam and gamma-ray irradiations were 1.72 and 1.79 kGy, respectively. The doses required for elimination of the spores could be lowered by using irradiation in combination with heat sterilization. When dextrin powder contaminated with 10(4) CFU/g of A. acidoterrestris was preirradiated at 1.0 kGy of electron beam, the citrus juice containing dextrin at a concentration of 10% (wt/vol) was completely sterilized by heating for 20 min at 95 degrees C.

Beverages↗
PubMed2002

Increased pre-therapeutic serum vascular endothelial growth factor in patients with early clinical relapse of osteosarcoma.

To investigate the clinical significance of circulating angiogenic factors, especially in association with early relapse of osteosarcoma, we quantified pre-therapeutic levels of vascular endothelial growth factor, basic fibroblast growth factor and placenta growth factor in the sera of 16 patients with osteosarcoma using an enzyme-linked immunosorbent assay. After a 1-year follow-up, the serum level of angiogenic factors was analysed with respect to microvessel density of the biopsy specimen and clinical disease relapse. The serum vascular endothelial growth factor levels were positively correlated with the microvessel density with statistical significance (P=0.004; Spearman rank correlation) and also significantly higher in seven patients who developed pulmonary metastasis than the remaining nine patients without detectable disease relapse (P=0.0009; The Mann-Whitney U-test). In contrast, the serum levels of basic fibroblast growth factor or placenta growth factor failed to show significant correlation with the microvessel density or relapse of the disease. Although there was no significant correlation between serum vascular endothelial growth factor levels and the tumour volume, the serum vascular endothelial growth factor levels were significantly higher in patients with a vascular endothelial growth factor-positive tumour than those with a vascular endothelial growth factor-negative tumour. These findings suggest that the pre-therapeutic serum vascular endothelial growth factor level reflects the angiogenic property of primary tumour and may have a predictive value on early disease relapse of osteosarcoma.

Adult↗
PubMed2002

Chromatin reprogramming of male somatic cell-derived XIST and TSIX in ES hybrid cells.

In mammalian somatic cells, the X chromosome is active in XY males, whereas one X chromosome is inactivated in XX females. On the active male X chromosome, the XIST and TSIX genes are transcribed in undifferentiated cells of pre-implantation embryos (undifferentiated state) and then down-regulated upon cell differentiation (differentiated state). To explore the epigenetic mechanism involved in the on-off switching of XIST and TSIX transcription in the active X chromosome, male somatic cells were hybridized with male embryonic stem (ES) cells. Fluorescence in situ hybridization analysis revealed that the XIST gene derived from somatic cells was derepressed, as shown by the advent of two pinpoint signals. This was confirmed by strand-specific RT-PCR of XIST and TSIX genes. To analyze changes in chromatin structure in the promoter regions of XIST and TSIX derived from somatic cells, histone tail modifications were studied by chromatin immunoprecipitation analysis. Histones H3 and H4, which were hypoacetylated in the somatic cells, were hyperacetylated in the hybrid cells, and histone H3 lysine 4, which was hypomethylated in the somatic cells, was hypermethylated in the hybrid cells, indicating that the reactivation of XIST and TSIX was linked with chromatin modifications. In the telomeric region of DXPAS34, acetylation of histones H3 and H4 was dependent on reactivation of XIST and TSIX, whereas histone H3 lysine 4 was constitutively methylated independent of the transcriptional activity of those genes. We propose that the chromatin reprogramming is linked with the resetting of the memory found in the process of choosing an active X chromosome.

Animals↗
PubMed2001

Nuclear reprogramming of somatic cells by in vitro hybridization with ES cells.

The resetting of a somatic epigenotype to a totipotential state has been demonstrated by successful animal cloning, via transplantation of somatic nuclei into enucleated oocytes. We have established an experimental system, which reproduces the nuclear reprogramming of somatic cells in vitro by fusing adult thymocytes with embryonic stem (ES) cells. Analysis of the lymphoid-cell-specific V-(D)-J DNA rearrangement of the T cell receptor and immunoglobin genes shows that the ES cells have hybridized with differentiated cells. In these ES cell hybrids, the inactivated X chromosome derived from a female thymocyte adopts some characteristics of an active X chromosome, including early replication timing and unstable Xist transcription. We also found that an Oct4-GFP transgene, which is normally repressed in thymocytes, is reactivated 48 hr after cell fusion. The pluripotency of the ES-thymocyte hybrid cells is shown in vivo, since they contribute to all three primary germ layers of chimeric embryos. The somatic DNA methylation pattern of the imprinted H19 and Igf2r genes is maintained in these hybrids, unlike hybrids between ES and EG (embryonic germ) cells in which the differential methylation is erased. Thus, ES cells have the capacity to reset certain aspects of the epigenotype of somatic cells to those of ES cells.

Animals↗
PubMed2001

Restoration of endogenous wild-type p53 activity in a glioblastoma cell line with intrinsic temperature-sensitive p53 induces growth arrest but not apoptosis.

p53 protein is a transcription factor involved in multiple tumor-suppressor activities including cell cycle control and apoptosis. TP53 gene is frequently mutated in glioblastoma, suggesting the importance of inactivation of this gene product in gliomagenesis. Restoration of p53 function in glioblastoma cell lines deficient for p53 has shown that p53 induces growth arrest or apoptosis depending on the cell line and vector used to transduce wild-type TP53 alleles. Considering that astrocytes grow and express p53, it is not clear whether these results reflect physiologic responses or the result of p53 overexpression in combination with cellular responses to viral vector infection. Here, we reassessed this issue using a glioblastoma cell line (LN382) that expresses an endogenous temperature-sensitive mutant p53. This cell line expresses TP53 alleles (100% as determined by a p53 transcriptional assay in yeast) mutated at codon 197 GTG (Val) > CTG (Leu). We found that the p53 protein in these cells acted as an inactive mutant at 37 degrees C and as a functional wild-type p53 below 34 degrees C as demonstrated by several lines of evidence, including (i) restoration of transactivating ability in yeast, (ii) induction of p53-modulated genes such as CDKN1(p21) and transforming growth factor-alpha, (iii) disappearance of accumulated p53 protein in the nucleus and (iv) decrease in steady state p53 protein levels. This temperature switch allowed p53 levels, which were close to physiological levels to dramatically reduce LN382 cell proliferation by inducing a G(1)/S cell cycle block, but not to induce apoptosis. The lack of apoptosis was considered to be a result of the low level p53 expression, because increasing wild-type p53 levels by adenoviral-mediated gene transfer caused apoptosis in these cells. The LN382 cell line will be extremely useful for investigations into the roles of p53 in cellular responses to a variety of stimuli or damages.

Apoptosis↗
PubMed2001

Phospholamban domain IB forms an interaction site with the loop between transmembrane helices M6 and M7 of sarco(endo)plasmic reticulum Ca2+ ATPases.

Transmembrane helix M6 of the sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA) has been shown to form a site of interaction with phospholamban (PLN). Site-directed mutagenesis was carried out in the cytoplasmic loop (L67) between M6 and M7 in SERCA1a to detect other SERCA-PLN binding sites. Mutants N810A, D813A, and R822A had diminished ability to interact functionally with PLN, but only D813A and R822A had reduced physical interaction with PLN. PLN mutants R25A, Q26A, N27A, L28A, Q29A, and N30A had enhanced physical interaction with wild-type (wt) SERCA1a, but physical interaction of these PLN mutants with SERCA1a mutants D813A and R822A was reduced about 2.5 fold (range 1.44-2.82). Exceptions were the interactions of PLN N27A and N30A with SERCA1a D813A, which were reduced by 7.3- and 5.8-fold, respectively. A superinhibitory PLN deletion mutant, PLNDelta21-29, had strong physical interactions with SERCA1a and with SERCA1a mutant D813A. Physical interactions with SERCA1a and mutant D813A were sharply diminished, however, for the PLN deletion mutant, PLNDelta21-30, lacking PLN N30. Physical interactions between SERCA1a and a PLN-cytochrome b(5) chimera containing PLN residues 1-29 were much stronger than those between a PLN-cytochrome b(5) chimera containing PLN residues 1-21 and lacking N27. These results suggest that a SERCA1-PLN interaction site occurs between L67 of SERCA1a and domain IB of PLN, which involves SERCA1a D813 and PLN N27 and N30.

Binding Sites↗
PubMed2001

Overexpression of homeobox gene HOXD3 induces coordinate expression of metastasis-related genes in human lung cancer cells.

Homeobox-containing genes are expressed in spatiotemporal fashion during embryogenesis and act as master transcription-regulating factors which control the expression of a variety of genes involved in morphogenesis. They are also expressed in a tissue-specific manner in normal adult tissues and appear to give cells spatial information in the maintenance of their architectural integrity. We transfected a HOXD3 class I homeobox-containing gene into human lung cancer A549 cells and investigated alterations in gene expressions and phenotypes related to the maintenance of tissue architecture in HOXD3-overexpressing A549 cells. In the HOXD3-overexpressing cell lines, expression of E-cadherin was lost and plakoglobin was strongly repressed, whereas integrin alpha3 and beta3 were up-regulated and N-cadherin and integrin alpha4 were newly expressed. Compared with parental and control transfectant lines, the HOXD3-overexpressing cell lines showed highly motile and invasive activity. Blocking experiments using anti-integrin beta1 and beta3 suggested that the increased haptotaxis of the HOXD3-overexpressing cells to vitronectin resulted from increased expression and activation of integrin alphavbeta3, and that overexpression of the HOXD3 gene converted the integrin beta1-dependent haptotaxis to fibronectin into both integrin beta1- and beta3-dependent one. HOXD3 overexpression increased production of matrix-degrative enzymes including matrix metalloproteinase-2 and urokinase-plasminogen activator. When the tumor cells were intravenously injected into the tail veins of nude mice, HOXD3 transfectants formed a significantly large number of metastatic foci in lungs compared with the control transfectants. These findings suggest that HOXD3 can act as a metastasis-promoting gene in human lung cancer A549 cells.

Antigens, CD↗
PubMed2001

Vertebrate gastrulation: calcium waves orchestrate cell movements.

A recent study reveals that the propagation of intercellular calcium signals is closely associated with the generation of convergent extension movements during Xenopus gastrulation. Such signals provide a mechanism whereby large populations of cells can communicate to generate orchestrated cell movements.

Animals↗
PubMed2001

Functional characterization of naturally occurring mutants (P405R and P425L) of p73alpha and p73beta found in neuroblastoma and lung cancer.

The novel candidate tumor suppressor p73, a structural and functional homolog of p53, activates various p53 responsive promoters and induces tumor cell apoptosis. Although p73 is infrequently mutated in human cancers, we have previously found two types of p73 mutation with amino acid substitution (P405R and P425L) in primary neuroblastoma and lung cancer. Here we report generations of the p73 mutants with either P405R or P425L substitution and functional analysis of these naturally occurring mutants. Indirect immunofluorescence staining revealed that nuclear accumulation of p73alpha or p73beta was not affected by these mutations. The P425L substitution reduced the ability of p73alpha to transactivate various p53 responsive promoters (p21(Waf1), Mdm2, and Bax). Moreover, this down-regulation was correlated with the reduced capability of p73alpha(P425L) to suppress cell growth in p53-deficient SAOS-2 cells. In contrast, p73beta(P425L) was as effective as wild-type p73beta in transactivation and growth inhibition. On the other hand, the P405R substitution had no significant effect on both the transcriptional activity and the growth-suppressive ability of p73alpha or p73beta. These results suggested that, at least, one of the naturally occurring p73 mutants, p73alpha(P425L), was a functionally defective mutant of p73.

Amino Acid Substitution↗
PubMed2001

Benzylic intermolecular carbon-carbon bond formation by selective anodic oxidation of dithioacetals.

[reaction: see text]. Novel anodic intermolecular carbon-carbon bond formation has been accomplished by the oxidative carbon-sulfur bond fission of benzylic dithioacetals to give a wide variety of aromatic compounds. The substitution reaction successfully took place by the selective anodic oxidation of a sulfur atom of a dithioacetal. Stepwise double-substitution reactions were also achieved by the regulation of oxidation potential.

Acetals↗