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A Okamoto

Publications and source records attributed to A Okamoto.

At least 37 records · Page 2Linked to original sources
PubMed2001

A newly developed bisphosphonate, YM529, is a potent apoptosis inducer of human myeloma cells.

We examined the effect of YM529, a newly developed third-generation bisphosphonate (BP), on the growth of human myeloma cell lines using the trypan blue dye exclusion test and Alamar blue assay. BPs induced inhibition of proliferation in all cell lines dose-dependently, and YM529 had a most potent growth inhibitory effect, followed by incadronate and pamidronate. Flow cytometric analysis using annexinV and 7AAD showed that YM529 most significantly induced apoptosis of all myeloma cell lines. These observations suggested that YM529 is a potent apoptosis inducer of myeloma cells, and might have some benefit not only on the improvement of bone lesions but also on survival in some myeloma patients.

Antineoplastic Agents↗
PubMed2001

Effects of adsorbent properties on zone spreading in expanded bed chromatography.

The mixing performance as well as the adsorption performance in expanded bed chromatography (EBC) was investigated by using various types of adsorption media (average particle size = 100-700 microm, density = 1100-1700 kg/m3, base matrix = hydroxyapatite, styrene-divinylbenzene, cross-linked agarose). The scale down study with 0.8 cm diameter columns was also attempted. Pulse response curves were measured with vitamin B12 as a tracer [Residence time distribution RTD experiments], and the HETP (height equivalent to a theoretical plate or plate height) values were calculated from the peak variance and the peak retention time. The HETP values for different types of packing media tested showed very similar values (0.5-1.0 cm), which did not depend on the flow-rate or the column diameter (0.8-2.6 cm). Dynamic binding capacity (DBC) values of lactic acid on a Dowex anion-exchange resin were determined from breakthrough curve (BTC) measurements for both EBC and fixed bed chromatography (FBC). The DBC values for EBC were similar to those for FBC. When the liquid feed contained insoluble particles (yeast cells) the degree of mixing increased. However, the contribution of the mixing to the total spreading of BTCs for EBC was usually small so that this increase in the mixing did not affect the adsorption performance or the DBC values significantly.

Adsorption↗
PubMed2001

Synthesis and evaluation of 1-arylsulfonyl-3-piperazinone derivatives as factor Xa inhibitor.

Intravascular clot formation is an important factor in a number of cardiovascular diseases. Therefore, the prevention of blood coagulation has become a major target for new therapeutic agents. One attractive approach is the inhibition of factor Xa (FXa), which is a key enzyme in coagulation cascade responsible for the generation of thrombin by limited proteolysis of its zymogen, prothrombin. We have investigated 1-arylsulfonyl-3-piperazinone derivatives, containing a 4-(piperidino)pyridine group in place of guanidino and/or amidino groups, and discovered compound M55113 (30a: 4-[(6-Chloro-2-naphthalenyl)sulfonyl]-1-[[1-(4-pyridinyl)-4-piperidinyl]methyl]piperazinone), as a potent inhibitor of FXa (IC50=0.06 microM) with high selectivity for FXa over trypsin and thrombin.

Anticoagulants↗
PubMed2001

Effectiveness of an antiplatelet agent for coronary artery ectasia associated with silent myocardial ischemia.

A 74-year-old Japanese male was referred to our hospital because of an abnormal electrocardiogram. The electrocardiogram revealed tall P waves in leads II, III, and aV(F). Echocardiography disclosed hypokinesis extending from the anteroseptal region to the apex. Iodine-123 15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (123-BMIPP) scintigraphy revealed reduced uptake from the anteroseptal region to the apex. Coronary arteriography demonstrated diffuse dilatation of the right and left coronary arteries without organic stenosis, and left ventriculography showed hypokinesis at the same area. Furthermore, the coronary flow reserve in the left anterior descending artery was decreased. He was treated with an antiplatelet agent. Ten months later, the left ventriculography, 123I-BMIPP scintigraphy findings and coronary flow reserve were normalized. These findings demonstrate that antiplatelet therapy may be useful in the preservation of left ventricular function in patients with coronary artery ectasia.

Aged↗
PubMed2001

Early relapse after high-dose chemotherapy rescued by tumor-free autologous peripheral blood stem cells in acute lymphoblastic leukemia: importance of monitoring for WT1-mRNA quantitatively.

A 24-year-old woman who suffered from ALL with MLL gene rearrangement received high-dose chemotherapy followed by autologous PBSC transplantation during complete remission (CR). Reverse transcriptase-polymerase chain reaction (RT-PCR) used to detect MLL/LTG4 chimeric mRNA showed no minimal residual disease (MRD) in the graft or bone marrow at the transplantation. However, the leukemia relapsed four months after transplantation. Retrospective analysis of quantitative measurement of Wilms tumor gene (WT-1) mRNA showed an increased level in the bone marrow although it was within the normal range. These observations suggest that careful monitoring of MRD by quantitative measurement of WT-1 mRNA in addition to disease-specific chimeric mRNA is required to predict relapse.

Adult↗
PubMed2001

Genetic alterations and expression of the protein phosphatase 1 genes in human cancers.

Recent studies have revealed that genetic alterations of the protein phosphatase genes, including PTEN, PPP2R1A, PPP2R1B and PPP1R3, are involved in human carcinogenesis. In the present study, we examined the genetic and expression status of nine protein phosphatase 1 (PP1) genes in 55 human cancer cell lines, consisting of 10 small cell lung cancers, 22 non-small cell lung cancers, 11 colorectal cancers, 7 gastric cancers and 5 ovarian cancers. The PP1 genes examined were three catalytic subunit genes, PPP1CA, PPP1CB and PPP1CC, and six regulatory subunit genes, PPP1R1A, PPP1R2, PPP1R5, PPP1R6, PPP1R7 and PPP1R8. Three catalytic subunit genes and three regulatory subunit genes, PPP1R2, PPP1R7 and PPP1R8, were ubiquitously expressed in the 55 cell lines, while PPP1R1A, PPP1R5, and PPP1R6 were differentially expressed. Possible missense mutations of the PPP1R5, PPP1R7 and PPP1R8 genes were detected in one (2%), two (4%) and one (2%) cell line, respectively. A rare, non-synonymous polymorphism was also identified in the PPP1R5 gene. Four of the 55 cell lines carried genetic alterations of several protein phosphatase genes, including PTEN, PPP1R3, PPP1R7 and PPP1R8. Ubiquitous expression as well as a lack of genetic diversity of catalytic subunit genes suggested the essential role of these genes for the growth of cancer cells. In contrast, differential expression, somatic mutations and/or genetic polymorphisms of several regulatory subunit genes indicate the involvement of these genes in multistep carcinogenesis.

DNA Primers↗
PubMed2001

Study of the fluoridated adhesive resin cement--fluoride release, fluoride uptake and acid resistance of tooth structures.

The objectives of this study, were to evaluate the fluoride release from fluoridate adhesive resin cement, fluoride uptake into surrounding tooth structures and the effect of their acid resistance. Several specimens were prepared using a plastic ring mould, from extracted human premolars, and prepared from enamel and dentin of the central area of the buccal surface of bovine teeth. The fluoride release rate of fluoridate adhesive resin cement (PN 200) per day was higher than other materials during the 7-day study period. Fluoride released and fluoride uptake by tooth structures was higher in the fluoridate adhesive resin cement. WDX analysis showed the fluoride concentration on dentin contact area was higher than that of enamel after 60 days of immersion in deionized water. The calcium release values were similar for enamel and dentin plates in the various test materials. The present findings indicated the important enhancement of tooth structure acid resistance by fluoridate material.

Animals↗
PubMed2001

Evaluation of the surface roughness of compomer by laser scanning microscopy.

The purpose of this study was to evaluate the effect of alcoholic and low pH soft drinks on the surface roughness of compomer restorative materials. There were five tested materials and four immersion media. Specimens were immersed in test solutions for a 10-day period at a temperature of 37 degrees C. Measurement of the surface texture was carried out using a laser scanning microscope (a non-contact laser stylus tracing method). This was also used to produce the Laser Scanning Microscope Image (LSM Image). Specimens immersed in orange juice and whisky displayed higher values for Ra & Rz than specimens immersed in soft drinks and deionized water. LSM Image showed a difference between the control and the examined side, especially for specimens immersed in low pH soft drinks this could be due to the erosive effect of the media. Alcoholic and low pH soft drinks caused deterioration of the materials surface, which may lead to a clinically detectable rough and dull surface.

Alcoholic Beverages↗
PubMed2001

Absence of p51 alteration in human ovarian cancer.

The p51 gene encodes a protein with significant homology to p53, thus, it is a candidate tumor suppressor gene. To investigate the involvement of the p51 gene in human ovarian carcinogenesis, p51 gene alterations were examined in primary ovarian cancers and ovarian cancer cell lines. Mutation analysis of the p51 gene was performed in 40 primary ovarian cancers and 6 ovarian cancer cell lines using the PCR-SSCP and direct sequencing methods. Expression of p51 mRNA was examined in 9 primary ovarian cancers and 5 ovarian cancer cell lines by Northern blot and RT-PCR analyses. No mutations of the p51 gene causing amino acid substitutions or frameshifts were detected in either primary tumors or cancer cell lines by PCR-SSCP analysis of the entire coding region, although several genetic polymorphisms were detected in three samples. Allelic imbalance was detected in 3 of 19 (16%) primary ovarian cancers. No p51 gene expression was detected in 9 primary ovarian cancers and the corresponding normal ovarian tissues by Northern blot and by RT-PCR analyses. One of 5 ovarian cancer cell lines showed p51 gene expression by Northern blot analysis (20%). These results indicated that p51 gene expression was silent in normal ovarian tissues and primary ovarian cancers, and that mutation of the p51 gene does not play a major role in the development of ovarian cancer.

Blotting, Northern↗
PubMed2001

[Clinicopathologic study on chronic pancreatitis with diffuse irregular narrowing of the main pancreatic duct].

We studied the clinicopathologic features of 13 cases of chronic pancreatitis with diffuse irregular narrowing of the main pancreatic duct (MPD). It occurs frequently in relatively elder men. Diffuse irregular narrowing of the MPD and stenosis of the common bile duct on ERCP, and swelling of the pancreas on US/CT were detected in all cases. An autoimmune mechanism might be involved in the etiology at least in 5 patients with hypergammaglobulinemia and positive autoantibodies. Surgical therapy was performed in 8 patients and 3 patients were treated with steroids. No patients showed recurrence of pancreatitis. Histologic findings were characterized by diffuse lymphoplasmacytic infiltration with marked interstitial fibrosis in the pancreas, obliterated phlebitis of the pancreatic veins. Similar inflammatory process involved the bile duct and the gallbladder. These histologic findings were similar to those of multifocal fibrosclerosis. Chronic pancreatitis with diffuse irregular narrowing of the MPD is overlapped with autoimmune pancreatitis in many cases, but may be a variant of multifocal fibrosclerosis involving the pancreas in some cases.

Adult↗
PubMed2001

[Therapy-related myeloid leukemia following platinum-based chemotherapy for ovarian cancer].

A 40-year-old woman, who had suffered from AML (M1) in 1983, developed ovarian cancer (stage IIIc) in December 1996 after long-term remission. She underwent surgical resection of the cancer, 10 courses of standard chemotherapy and tandem PBSCT (total dose: CBDCA 6,750 mg, CDDP 200 mg, CPA 16,000 mg, THP-ADR 450 mg). After receiving the last course of chemotherapy in June 1998, she was referred to our hospital in September 1998 because of pancytopenia. Laboratory findings showed pancytopenia with 34% leukemic cells, which were positive for alpha NBE and negative for POX and CAE. Surface-marker analysis of the leukemic cells showed positivity for CD11c, CD33, CD56, and DR, and chromosome analysis revealed 47, XX, +8. The patient was diagnosed as having AML (M5a), and received induction therapy consisting of IDR and Ara-C, which led to complete remission. As she had not received etoposide, this case was thought to have been therapy-related leukemia due to the platinum agents used for treating the ovarian cancer.

Adult↗
PubMed2000

Identification by cDNA microarray of genes involved in ovarian carcinogenesis.

To identify genes involved in the development or progression of ovarian cancer, we analyzed gene expression profiles of nine ovarian tumors using a DNA microarray consisting of 9121 genes. Comparison of expression patterns between carcinomas and the corresponding normal ovarian tissues enabled us to identify 55 genes that were commonly up-regulated and 48 genes that were down-regulated in the cancer specimens. When the five serous adenocarcinomas were analyzed separately from the four mucinous adenocarcinomas, we identified 115 genes that were expressed differently between the two types of tumor. Investigation of these genes should help to disclose the molecular mechanism(s) of ovarian carcinogenesis and define molecular separation of the two most common histological types of ovarian cancer.

Adenocarcinoma, Mucinous↗
PubMed2000

Transcriptional regulation of the ATP citrate-lyase gene by sterol regulatory element-binding proteins.

In an attempt to identify unknown target genes for SREBP-1, total RNA from a stable Chinese hamster ovary cell line (CHO-487) expressing a mature form of human SREBP-1a (amino acids 1-487) with a LacSwitch Inducible Mammalian Expression System was subjected to a polymerase chain reaction subtraction method. One of the fragments was found to have 90 and 86% homology with rat and human ATP citrate-lyase (ACL) cDNA, respectively. When Hep G2 cells are cultured under either sterol-loaded or -depleted conditions, expression of the gene is induced approximately 2-3-fold by sterol depletion. To investigate the direct effect of SREBP-1a on transcription, luciferase assays using the promoter of the human ACL gene were performed. These deletion studies indicated that a minimum 160-base pair segment contains the information required for the transcriptional regulation brought about by enforced expression of SREBP-1a. Luciferase assays using mutant reporter genes revealed that SREBP-dependent transcriptional regulation is mediated by two nearby motifs, the SREBP-binding site (a TCAGGCTAG sequence) and the NF-Y-binding site (a CCAAT box). It was confirmed by gel mobility shift assays that recombinant SREBP-1a binds to the sequence. Data from studies with transgenic mice and reporter assays show that the ACL gene promoter is activated by SREBP-1a more strongly than SREBP-2 in contrast to the HMG CoA synthase and LDL receptor gene promoters, which exhibit the same preference for the two factors. Therefore, SREBPs transcriptionally regulates ACL enzyme activity, which generates the cytosolic acetyl CoA required for both cholesterol and fatty acid synthesis.

ATP Citrate (pro-S)-Lyase↗
PubMed2000

Somatic mutations and genetic polymorphisms of the PPP1R3 gene in patients with several types of cancers.

Recently, we found nonsense and missense mutations of the PPP1R3 (protein phosphatase 1, regulatory subunit 3) gene in diverse human cancer cell lines and primary lung carcinomas, indicating that PPP1R3 functions as a tumor suppressor in human carcinogenesis. In this study, to assess the prevalence of PPP1R3 mutations in human primary cancers and the genetic diversity of the PPP1R3 gene in the human population, somatic mutations and genetic polymorphisms in the PPP1R3 gene were examined in 137 pairs of cancerous and non-cancerous tissues of patients with cancers of colon, ovary, and liver. Five somatic mutations including two missense mutations were detected in three cancerous tissues consisting of two colorectal carcinomas and one ovarian carcinoma. Five novel single nucleotide polymorphisms (SNPs) associated with the substitution of amino acids were also identified in cancer patients, in addition to five known nonsynonymous SNPs, including three previously reported ones as having an impact on the susceptibility to insulin resistant disorders. Differences in the activities and properties of multiple PPP1R3 proteins, which are produced in human cells due to variable somatic mutations and genetic polymorphisms in the PPP1R3 gene, can be involved in human carcinogenesis and susceptibility to diseases.

Amino Acid Substitution↗
PubMed2000

Allelic imbalance and mutations of the PTEN gene in ovarian cancer.

The PTEN/MMAC1/TEP1 tumor-suppressor gene, which maps to chromosome 10q23.3, is mutated and homozygously deleted in a variety of human tumors, including endometrioid-type ovarian tumors. We examined 33 primary ovarian cancers and 3 ovarian borderline tumors for allelic imbalance (AI) of the 10q23.3 region using 5 polymorphic markers, including an insertion/deletion-type polymorphic marker identified in intron 4 of the PTEN gene. AI at one or more loci was detected in 12 of 31 (39%) informative ovarian cancers and none of 3 ovarian borderline tumors. The commonly deleted region was mapped between the D10S215 and D10S541 loci, including the PTEN locus. Moreover, the incidence of AI at the PTEN locus (38%) was the highest among the 5 loci examined. Therefore, we searched for mutations in the entire coding region of the PTEN gene by PCR-SSCP and sequencing analyses in these tumors and 7 ovarian cancer cell lines. Mutations were detected in 3 of the 33 (9%) ovarian cancers: 2 cases with double mutations and 1 case with a mutation on 1 allele accompanied by deletions on both alleles in the poly T tract preceding the splice acceptor site in intron 7. An intragenic deletion was detected in 1 of the 7 (14%) ovarian cancer cell lines. PTEN mutations were detected not only in the endometrioid type but also in the serous and mucinous types of ovarian cancer. However, PTEN was not mutated in the 12 tumors that showed AI of the PTEN locus. Our results suggest that the PTEN gene plays an important role in the development of a subset but diverse histological types of ovarian tumors. However, it is possible that another tumor-suppressor gene in the close vicinity of the PTEN gene is also inactivated by AI of the 10q23.3 region.

Chromosome Mapping↗
PubMed2000

Synthesis and antitumor activity of duocarmycin derivatives: modification at the C-7 position of segment-A of A-ring pyrrole compounds.

A series of the C7-substituted A-ring pyrrole derivatives of duocarmycin were synthesized, and evaluated for in vitro anticellular activity against HeLa S3 cells and in vivo antitumor activity against murine sarcoma 180 in mice. All of the C7-substituted A-ring pyrrole compounds decreased potency in vitro and in vivo. However, some showed strong antitumor activity with T/C values less than 0.3. Among them, the 7-formyl compound 5d showed remarkable potent in vivo antitumor activity and low peripheral blood toxicity, which were equal to 2c.

Animals↗