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Biomedical subjects

F Ishikawa

Publications and source records attributed to F Ishikawa.

At least 73 records · Page 4Linked to original sources
PubMed1998

[Structure and regulation mechanisms of telomerase].

Telomerase is a specialized type of reverse transcriptase which catalyzes the synthesis of telomeric DNA using intrinsic RNA as a template. The enzyme was originally found in a ciliate Tetrahymena, and has been extensively investigated using ciliates or budding yeast. In mammals, the enzyme is highly active in most cancer cells and germ cells, but is inactive in most somatic cells, suggesting the activation of telomerase may be important for the continued cell growth or progression of cancer cells. Recently, two protein components of the mammalian telomerase have been identified using homology to the sequencing data from unicellular eukaryotes. Interestingly, telomerase activity was induced by the expression of catalytic subunit, hTERT, in telomerase-negative normal fibroblast cells, indicating that it plays a key role in the activation of telomerase in cancer cells.

Animals↗
PubMed1998

[Chromosome rearrangement involving telomeres in cancers].

Stable maintenance of chromosomes needs the functional telomeres at the chromosomal ends. It has been proposed that the loss of telomeric function (LTF) plays a major role in the production of abnormal chromosomes, such as the telomere association (TA) and the jumping translocation (JT). We analyzed TA and JT to evaluate the involvement of LTF in chromosomal instability. A shortened telomeres was identified at the fusion point of the JT. We also developed a method to examine TA based on PCR and found relationships between telomere shortening and products of PCR. Our findings strongly suggest that LTF may cause chromosomal instability and contribute to cancer cell evolution.

Chromosome Aberrations↗
PubMed1997

Comparative gene mapping of the human and mouse TEP1 genes, which encode one protein component of telomerases.

The chromosomal locations of the human TEP1 (telomerase protein component 1) and mouse Tep1 genes, which were originally named TLP1 (telomerase protein 1) or TP1 (telomerase-associated protein 1), were determined by direct R-banding FISH and a molecular linkage analysis with interspecific backcross mice. The human TEP1 and mouse Tep1 genes were mapped by FISH to human chromosome 14q11.2 and to the C2D1 band of mouse chromosome 14, respectively. By means of genetic linkage mapping, the mouse gene was further localized as being 2.7 cM distal to D14Mit18 and D14Mit134 and 2.0 cM proximal to D14Mit5 on mouse chromosome 14, where conserved linkage homology with human chromosome 14q11-q12 has been identified.

Animals↗
PubMed1997

TLP1: a gene encoding a protein component of mammalian telomerase is a novel member of WD repeats family.

We have cloned and characterized the rat telomerase protein component 1 gene (TLP1), which is related to the gene for Tetrahymena p80. The cDNA encodes a 2629 amino acid sequence and produces the TLP1 proteins p240 and p230. The anti-TLP1 antibody specifically immunoprecipitated the telomerase activity. Moreover, p240 and p230 were copurified with telomerase activity in a series of extensive purification experiments. These results strongly suggest that the TLP1 proteins are components of, or are closely associated with, the rat telomerase. A pulse-chase experiment showed that p240 is modified to p230 in vivo. p230 was the dominant form in telomerase-positive cells, suggesting that modification of the TLP1 protein may regulate telomerase activity in vivo.

Animals↗
PubMed1997

Telomere crisis, the driving force in cancer cell evolution.

Cancer cells show characteristic telomere dynamics. Their chromosomes usually have short telomeres and a high telomerase activity. The "telomere crisis model" proposed here suggests that these unique telomeric features are responsible for the progression of cancer.

Blotting, Southern↗
PubMed1997

Telomere crisis in leukemia.

Previous studies on telomere dynamics in leukemia are summarized. The 'telomere crisis model' is proposed to explain the clonal evolution mechanism of cancer cells from the standpoint of telomere biology. Future trends, including the development of potential telomerase inhibitors as a new class of anti-cancer agent, are discussed.

DNA Damage↗
PubMed1997

Regulation mechanisms of mammalian telomerase. A review.

In this review, I summarize the most recent progress in the studies on mammalian telomerase, especially focusing on the molecular aspects. Possible regulation mechanisms of telomerase activity in mammalian cells are discussed.

Animals↗
PubMed1996

A novel quantitative 'stretch PCR assay', that detects a dramatic increase in telomerase activity during the progression of myeloid leukemias.

Telomerase activation is important for carcinogenesis. However, the timing and magnitude of the activation during cancer development are unknown. In this study, a new PCR-based method for measuring telomerase activity was developed and shown to be very useful for quantitative analysis of human telomerase. Using this assay, blood or bone marrow cells from healthy donors, and patients with chronic myelogenous leukemia (CML) and acute myelogenous leukemia (AML) were examined as to their relative activity. Telomerase activity present in normal peripheral blood cells was generally very low. However, significant activity was detected occasionally in samples derived from younger healthy donors. Striking telomerase activation was observed at the time of the blastic crisis in CML: no samples from chronic phase cases showed significant activity, while all cases with a well established crisis showed strong activity. Most AML cases were telomerase-positive. Quantitative analyses revealed that the relative titer varied among the AML patients, from as low as found in normal cells to as high as found in cell lines. However, a tendency that the activity was higher in relapsed cases than in fresh ones was suggested. In summary, telomerase was activated during the progression of the clinical stages in leukemias. This observation suggests that shortened telomeres and increased telomerase activity might be necessary for cancer cells to undergo clonal evolution towards more malignant phenotypes in advanced stages.

Adult↗
PubMed1996

[A case of hemolysis induced by lansoprazole].

Hemolytic anemia and possible aplastic crisis with symptoms including jaundice, general fatigue and dark urine developed in a man being treated only by lansoprazole. Five days later, he was treated with antibiotics. The next day, he was admitted to our hospital because of jaundice. On admission, the hemoglobin was 14.0 g/dl, reticulocyte count 8/1000, platelets 79 x 10(9)/l and total bilirubin 12.4 mg/dl (indirect bilirubin 9.5 mg/dl). The above medications were discontinued. The direct Coombs antiglobulin test was positive. Examination of the complement revealed a C3 fiter at the upper limit of normal and an increased C4 and CH50. Three days after admission, he had a severe anemia. The hemoglobin was 3.3 g/DL. We thought it possible that aplastic crisis had followed the hemolytic anemia induced by lansoprazole. He was treated with blood transfusions and corticosteroids. He recovered from anemia within three weeks. Exhaustive studies to identify the cause of the hemolytic anemia were undertaken with negative results. We detected IgG antibody to lansoprazole. We believe that the hemolytic anemia was induced by lansoprazole.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1996

[Telomere and telomerase].

Telomeres are the functional domains positioned at the ends of chromosomes. It is essential for the stable maintenance of chromosomes. Telomerase is an enzyme that has an important role in the DNA replicator at telomeres. Its activity is specifically activated in cancer cells. We have reported a novel specific and sensitive assay (stretch RCR assay) for the detection of telomerase activity. We analyzed the telomerase activity in leukemias using this method. The results showed that telomerase is specifically activated during the progression stages of leukemia. The "telomere crisis model" has been proposed for explaining the role of the telomere dynamics in malignancies.

DNA Replication↗
PubMed1995

Bioluminescent detection of RNA with sequence-specificity using RNA binding protein-luciferase fusion protein.

A novel bifunctional reagent has been synthesized for RNA detection by genetic fusion of a sequence-specific RNA binding protein and firefly luciferase. The RNA binding protein used in this study recognizes the oligoribonucleotide rH4 which contains four (UUAGGG)-repeat sequence, while luciferase works as a bioluminescent marker. The constructed fusion protein exhibited both sequence-specific RNA binding and bioluminescent activities. The rH4 and rECGF, which has an unrelated sequence having the same length as rH4, were immobilized on a nylon membrane. The membrane was pre-treated by 5% bovine serum albumin and soaked into a fusion protein solution. Bioluminescent detection has successfully been performed at more than 50 pmol of rH4, so the detection limit using this protein was 50 pmol. However, no appreciable bioluminescence was induced by rECGF.

Base Sequence↗