Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.10.2 (focal adhesion kinase)
44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Polymerase chain reaction (PCR) is a novel tool for the in vitro amplification of DNA segments up to several kb. Repeated cycles of DNA synthesis by heat-stable Taq DNA polymerase enables to obtain more than 10(5) copies of the target sequence. Recently its enormous attitude of amplification has been applied for the detection of tumor-specific gene alterations. Examples include the detection of point mutation of RAS oncogenes at codons 12, 13, and 61 and the detection of minimal residual neoplastic cells in patients in complete clinical remission. Among many kinds of tumor specific gene translocations, BCR-ABL gene in t(9;22)(q34;q11) and BCL-2-IgH gene in t(14:18)(q32;q21) have been successfully PCR-amplified around their fused regions. In lymphoid malignancies gene rearrangements of T cell receptor chain or immunoglobulin heavy chain can be used as clonal markers for leukemic cells. PCR technique permits the detection of leukemia DNA at dilution of 10(-4) to 10(-6). Although further investigation of patients' follow-up in large scale is needed, this technique seems to hold promise for the monitoring of residual neoplastic cells.
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PMID:[Polymerase chain reaction (PCR)--a novel tool for the molecular diagnosis of neoplasms]. 220 61

The Philadelphia chromosome (Ph1) is present in 95% of chronic myelogenous leukaemias (CML) and 15% of acute lymphoblastic leukaemias (ALL). This cytogenetic marker is due to a t(9;22) translocation, which causes a rearrangement of the ABL oncogene. In order to better define the relationship between type of genomic rearrangement, variant ABL protein expressed and haematological phenotype, a series of Ph1-positive acute leukaemias, both myeloblastic (AML) and lymphoblastic, and several CML lymphoid blast crises have been analysed at the DNA and protein level. The results confirm the presence of the ABL protein P210 in all cases of CML, ALL and AML positive for rearrangement in the bcr region of chromosome 22, and, surprisingly, in one AML case apparently negative for bcr rearrangement. The ABL protein P190 was found to be present only in cases of ALL negative for bcr rearrangement. Polymerase chain reaction (PCR) analysis of the types of 9/22 junctions present in the mRNA of CML lymphoid blast crises showed no evidence of 'ALL-type' transcripts.
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PMID:ABL proteins in Philadelphia-positive acute leukaemias and chronic myelogenous leukaemia blast crises. 222 47

Chronic myelogenous leukemia (CML) is characterized by the presence of a novel fusion gene comprised of portions of the BCR gene from chromosome (ch) 22 and the ABL gene from ch 9. The present study was designed to identify regulatory DNA regions as determined by DNAase I hypersensitivity to address the question of whether altered chromatin contributes to changes in ABL expression. We identify five hypersensitive (HS) sites within the abnormal BCR/ABL allele in K562 cells in a pattern different from the normal BCR. The pattern of hypersensitivity is modified when the cells undergo hemin induced differentiation. These results indicate that the normal BCR has a chromatin configuration consistent with active transcription and that the BCR/ABL fusion gene chromatin is different. This may be important in the pathogenesis of CML.
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PMID:Chromatin alterations surrounding the BCR/ABL fusion gene in K562 cells. 226 34

The subrenal capsule assay for cancer chemotherapy was performed, using tumor-specimens of 19 patients' cancers. Twelve tumor-specimens were implanted simultaneously under the renal space of immunocompetent CDF1 mice, cyclosporin A (CsA) 60 mg/kg treated mice, and BALB/c-nu/nu (nude) mice. The persistence and growth of implanted tumor-xenografts of each mouse, was evaluated, on day 6 and 9 after inoculation. The tumor-xenografts implanted under the renal space of immunocompetent mice, grew larger on days 6 in 9 cases, but histological evaluation showed tumor tissues were in various degree replaced by host reactive tissues. Host reaction in CsA-treated mice or nude mice was suppressed almost completely, but the persistence and proliferation of tumor-xenografts of both mice was varied, depending on the nature of original tumors. The judgment for cancer chemotherapy on our modified SRC assay was almost similar between CsA-treated mice and nude mice, but there were some cases in which macroscopical judgment didn't correspond with histological effect. The DNA synthesis of tumor-xenografts of 7 patients, was examined by using sequential changes of BrdU labeling index (LI) in the renal space of CsA-treated mice. It was showed LI rather indicated the nature of original tumors itself.
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PMID:[The persistence and proliferation of tumor-xenografts implanted under the renal capsule of immunocompetent mice, cyclosporin A-treated mice and nude mice]. 235 85

EMT 6/Ca/VJAC cells have been treated with various doses of bleomycin and the effects of these treatments in terms of cell killing and DNA damage have been determined. The experiments have been carried out with exponentially growing and plateau-phase cultures. Dose-response curves have been obtained using a clonogenic cell survival assay. Bleomycin-induced DNA damage was quantitated by a fluorescence procedure, based upon the time-dependent partial unwinding of cellular DNA under alkaline conditions. Although cells in exponential-phase of culture growth were more sensitive to bleomycin than those in plateau-phase, this could only be attributed to enhanced drug-DNA interaction at high (greater than 40 micrograms/ml) drug concentration. Thus factors other than DNA damaging potential and related to culture growth status control drug sensitivity.
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PMID:Dependence of bleomycin-induced cytotoxicity and DNA damage on the in vitro culture growth phase of mouse tumour cells. 244 99

In the male rat kangaroo cell line PTK2, argon laser (514.5 nm) microirradiation of both nucleoli in interphase cells 30, 23, and 12 h before mitosis, and nucleoli in early prophase cells resulted in the formation of micronucleoli, i.e., several small nucleolus-like bodies, in daughter cells. The irradiated cells were stained with methylene blue, which indicated that the nucleolar RNA was destroyed by laser microirradiation. Feulgen staining was applied to the irradiated cells in combination with the measurements of an MPV-II model microphotometer. Irradiated nucleoli were negative for DNA-Feulgen stain, which indicated that nucleolar DNA was destroyed by laser irradiation, so the nucleolar organizer gene was destroyed. After the nucleoli had been irradiated, the cells were continuously incubated at 37 degrees C for 12 and/or 24 h, then fixed and stained with AgNO3. Most of the nucleoli irradiated silver-stained negative that demonstrated that when the nucleoli were irradiated, rDNA was destroyed and transcription stopped. However, some silver grains were found in the nucleoplasm, whereas the nucleoli were silver-stained negative. The results suggest that subsidiary nucleolar organizer loci might exist scattered throughout the genome.
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PMID:Study on mechanism of micronucleoli formation by laser microirradiation. 247 12

Body weight gain (BWG), food intake, food efficiency rate (FER: food intake, g/protein intake, g), gastrocnemius muscle and liver weights, protein, RNA and DNA contents of gastrocnemius muscle and liver have been measured in growing rats (80-90 g initial body weight) fed ad libitum over a period of 11 days on 12.00% protein diets containing either heated and defatted Glycinae sojae (HSB) as control or the raw legume Vicia ervilia as the main sources of protein. It has been found that, as compared to HSB-fed rats, those fed the legume Vicia ervilia diet exhibited a significant reduction in growth, PER, FER, as well as, in RNA-activity (protein, g/day/RNA, g) and RNA/DNA ratio in both muscle and liver. Protein synthesis capacity (PSC:RNA, microgram/protein, mg), was found significantly increased in liver but not in muscle. The possible nature of these findings is discussed.
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PMID:Effect of the raw legume Vicia ervilia on muscle and liver protein metabolism in growing rats. 248 17

We report the sublocalization of the breakpoint in chromosome 22 in 33 patients with chronic myeloid leukemia (CML) who also had unusual marrow cytogenetics. In 23 patients, the leukemic clones were characterized by Philadelphia (Ph1) chromosomes that arose through complex translocations that involved three or more chromosomes. In the remaining ten patients, there were no detectable Ph1 chromosomes despite molecular evidence for the presence of rearrangements in the major breakpoint cluster region (bcr) of chromosome 22 in all cases. There was no significant difference between the two groups with respect to location of the breakpoints within the bcr. When these two groups of patients were combined, there was a significant excess of breakpoints in one segment of the bcr when compared to the distribution of breakpoints seen in 119 patients with simple 9;22 translocations. The difference in breakpoint distributions did not appear to be entirely attributable to differences between groups in disease duration at the time of study. These data support the notion that the unusual genetic recombinations that give rise to BCR/ABL fusion genes in CML involve specific DNA sequences of BCR (and possibly ABL) and additional, recombinogenic sequences, at least some of which are present in loci known to be nonrandomly involved in complex Ph1 translocations.
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PMID:Location of breakpoints within the major breakpoint cluster region (bcr) in 33 patients with bcr rearrangement-positive chronic myeloid leukemia (CML) with complex or absent Philadelphia chromosomes. 248 42

The region required for regulation of a previously characterized arginine-regulatable promoter upstream from the argC gene in the argCAEBD-cpa-argF cluster of Bacillus subtilis was defined by integration of argC-lacZ translational fusions into the chromosome at a site distant from the arginine loci. Some sequence similarity was detected between the argC regulatory region and the well-characterized Escherichia coli arginine operators (ARG boxes). This similarity was shown to be functional in vivo in that the B. subtilis repressor regulated the E. coli arginine genes, but the E. coli repressor, even when encoded by a multicopy plasmid, could not repress the B. subtilis argC promoter. In vitro binding studies using purified repressors on DNA fragments encoding operators from both E. coli and B. subtilis demonstrated interactions by both proteins.
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PMID:Sequences required for regulation of arginine biosynthesis promoters are conserved between Bacillus subtilis and Escherichia coli. 249 96

Sequence comparisons were made from 2214 bp of mitochondrial DNA cloned from six Pacific salmonid species. These sequences include the genes for ATPase subunit 6, cytochrome oxidase subunit 3, NADH dehydrogenase subunit 3, NADH dehydrogenase subunit 4L, tRNA(GLY), and tRNA(ARG). Variation is found at 338 silent and 12 nonsilent positions of protein coding genes and 10 positions in the two tRNA sequences. A single 3-bp length difference was also detected. In all pairwise comparisons the sequence divergence observed in the fragment was higher than that previously predicted by restriction enzyme analysis of the entire molecule. The inferred evolutionary relationship of these species is consistent between methods. The distribution of silent variation shows a complex pattern with greatly reduced variation at the junctions of genes. The variation in the tRNA sequences is concentrated in the DHU loop. The close relationship of these species and extensive sequence analyzed allows for an analysis of the spectrum of substitutions that includes the frequencies of all 12 possible substitutions. The observed spectrum of substitutions is related to potential pathways of spontaneous substitution. The salmonid sequences show an extremely high ratio of silent to replacement substitutions. In addition the amino acid sequences of the four proteins coded in this fragment show a consistently high level of identity with the Xenopus sequences. Taken together these data are consistent with a slower rate of amino acid substitution among the cold-blooded vertebrates when compared to mammals.
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PMID:Variation in salmonid mitochondrial DNA: evolutionary constraints and mechanisms of substitution. 255 Jun 57


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