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

---

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

We examined all reports of adult AIDS cases made to the 2 national surveillance centres in the UK for changes in AIDS defining conditions between January 1982 and September 1994. Differences and changes among persons diagnosed since January 1988 who had and had not been aware of their HIV infection prior to their AIDS diagnosis were of particular interest. Pneumocystis carinii pneumonia (PCP) is the AIDS defining disease most often reported at the initial AIDS diagnosis. Its proportion of all AIDS cases has increased significantly between January 1982 and December 1987 and decreased markedly thereafter. Since January 1988 a significant decrease in the proportion of cases diagnosed with cryptosporidial infection was also observed while increases were observed in the proportion of cases diagnosed with: HIV wasting (chi(1)(2) = 5.56) PML (chi(1)(2) = 19.47), mycobacterium avium complex (chi(1)(2) = 35.76) and pulmonary tuberculosis (chi(1)(2) = 144.0). For cases diagnosed between January 1988 and September 1994, PCP was more likely to be diagnosed in patients previously unaware of their HIV infection (P < 0.01) as was extrapulmonary TB (P < 0.01). In contrast, the following diseases were more likely to be diagnosed in patients already aware of their HIV infection prior to the diagnosis of AIDS: oesophageal candidiasis (P < 0.001), HIV wasting (P = 0.07), mycobacterium avium complex (P = 0.0001), cytomegalovirus disease (P < 0.001), HIV encephalopathy (P = 0.0009) and cryptosporidial infection (P = 0.02). Prophylaxis and anti-retroviral therapy appear to have had a significant impact on the temporal changes of the most frequently diagnosed AIDS diseases. While PCP prophylaxis has substantially reduced the likelihood of a PCP diagnosis at AIDS, the corresponding increase in other opportunistic infections suggests that there may be a need for improved prophylaxis for these conditions.
Int J STD AIDS 1996 Jul
PMID:AIDS defining diseases in the UK: the impact of PCP prophylaxis and twelve years of change. 887 55

Fluorescent in situ hybridization (FISH) is a rapid, sensitive and reliable method for the identification of complete chromosomes, or segments of them, during metaphase or nuclear interphase. The present study shows the results of the analysis of 32 bone marrow aspirates from patients with malignant hematological diseases (11 AML, 7 ALL, 12 CML and 2 CLL), referred to the Medical Genetics Unit of the Faculty of Medicine, Zulia University, Maracaibo, Venezuela between 1994 and 1996. All samples were studied by conventional and molecular techniques (FISH), using probes of total chromosomes, alpha-satellites and locus specific. In patients with AML and ALL and FISH technique detected clonal chromosomal abnormalities, that were not found by the conventional cytogenetic technique. Furthermore, the PML-alpha RARA complex was identified in the promyelocytic acute leukemias. The presence of the molecular complex ABL-BCR was also demonstrated in CML. The present study demonstrates the usefulness of the FISH technique in the detection of clonal chromosomal abnormalities, which are important when considering the clinical care of patients with these pathologies.
...
PMID:[Clonal chromosome abnormalities in malignant hematological diseases using fluorescence in situ hybridization]. 970 20

We investigated parental origin of rearranged chromosomes 9 and 22 (9q + and 22q -) in five patients with Ph-positive chronic myeloid leukemia (CML) using the C-banding and silver-staining methods of nucleolus organizer regions, respectively; of rearranged chromosome 21 (21q +) in seven patients with t(8;21)-positive acute myeloid leukemia (AML); and of rearranged chromosome 15 (15q +) in six patients with t(15;17)-positive AML. It was found that these rearranged chromosomes can be of either paternal or maternal origin. Although the number of patients examined was small, these results indicate that the genes rearranged as a result of these chromosome translocations (ABL, BCR, AML-1 and PML) are not genomically imprinted.
...
PMID:No parental origin bias for the rearranged chromosomes in myeloid leukemias associated with t(9;22), t(8;21) and t(15;17). 971 10

The mechanisms whereby chromosomal translocations are consistently associated with specific tumor types are largely unknown. A generally accepted hypothesis is that the physical proximity of the involved chromosomal regions may be one important factor in the genesis of these phenomena. Accordingly, a likely possibility is that such a proximity may occur in a cell-lineage and cell-differentiation stage-specific manner. In this work, we have addressed this issue using as models the ABL and BCR genes of t(9;22) and the PML and RARalpha genes of t(15;17). By using in situ hybridization and confocal microscopy, we have measured the distances between these two pairs of genes in three-dimensionally preserved hematopoietic cells belonging to different cell lineages, at various stages of differentiation, and at various stages of the cell cycle, with the following results. (1) Intergenic distances vary periodically during the cell cycle and a significant association of ABL with BCR and of PML with RARalpha is seen at the transition between S and G2, which persists during G2 and prophase (such a behavior is not observed for distances between ABL or PML and the beta-globin genes, used as a control). (2) The proportion of cells in which PML and RARalpha or ABL and BCR are closely associated is higher in hematopoietic precursors than in B-lymphoid cells (whereas the distances between ABL or PML and the beta-globin genes are not affected by cell type). (3) When intergenic distances in unstimulated bone marrow CD34(+) cells were compared with those in CD34(+) cells treated with interleukin-3 (IL-3), a trend towards a higher proximity of the ABL and BCR genes in the former and of the PML and RARalpha genes in the latter is observed. (4) Analysis of B-lymphoid cells during mitosis shows that intergenic distances at metaphase are strongly influenced by physical constraints imposed by the chromosomal location of the gene, by the size of the respective chromosome, and by the geometry of the metaphase plate. These findings suggest that intrinsic spatial dynamics, established early in hematopoiesis and perpetuated differentially in distinct cell lineages, may facilitate the collision of individual genes and thus reciprocal recombination between them at subsequent stages of hematopoietic differentiation.
...
PMID:The nuclear topography of ABL, BCR, PML, and RARalpha genes: evidence for gene proximity in specific phases of the cell cycle and stages of hematopoietic differentiation. 1045 98

Prospective studies on the detection of minimal residual disease (MRD) in acute leukemia patients have shown that large-scale MRD studies are feasible and that clinically relevant MRD-based risk group classification can be achieved and can now be used for designing new treatment protocols. However, multicenter international treatment protocols with MRD-based stratification of treatment need careful standardization and quality control of the MRD techniques. This was the aim of the European BIOMED-1 Concerted Action 'Investigation of minimal residual disease in acute leukemia: international standardization and clinical evaluation' with participants of 14 laboratories in eight European countries (ES, NL, PT, IT, DE, FR, SE and AT). Standardization and quality control was performed for the three main types of MRD techniques, ie flow cytometric immunophenotyping, PCR analysis of antigen receptor genes, and RT-PCR analysis of well-defined chromosomal aberrations. This study focussed on the latter MRD technique. A total of nine well-defined chromosome aberrations with fusion gene transcripts were selected: t(1;19) with E2A-PBX1, t(4;11) with MLL-AF4, t(8;21) with AML1-ETO, t(9;22) with BCR-ABL p190 and BCR-ABL p210, t(12;21) with TEL-AML1, t(15;17) with PML-RARA, inv (16) with CBFB-MYH11, and microdeletion 1p32 with SIL-TAL1. PCR primers were designed according to predefined criteria for single PCR (external primers A <--> B) and nested PCR (internal primers C <--> D) as well as for 'shifted' PCR with a primer upstream (E5' primer) or downstream (E3' primer) of the external A <--> B primers. The 'shifted' E primers were designed for performing an independent PCR together with one of the internal primers for confirmation (or exclusion) of positive results. Various local RT and PCR protocols were compared and subsequently a common protocol was designed, tested and adapted, resulting in a standardized RT-PCR protocol. After initial testing (with adaptations whenever necessary) and approval by two or three laboratories, the primers were tested by all participating laboratories, using 17 cell lines and patient samples as positive controls. This testing included comparison with local protocols and primers as well as sensitivity testing via dilution experiments. The collaborative efforts resulted in standardized primer sets with a minimal target sensitivity of 10-2 for virtually all single PCR analyses, whereas the nested PCR analyses generally reached the minimal target sensitivity of 10-4. The standardized RT-PCR protocol and primer sets can now be used for molecular classification of acute leukemia at diagnosis and for MRD detection during follow-up to evaluate treatment effectiveness.
...
PMID:Standardized RT-PCR analysis of fusion gene transcripts from chromosome aberrations in acute leukemia for detection of minimal residual disease. Report of the BIOMED-1 Concerted Action: investigation of minimal residual disease in acute leukemia. 1060 11

Fluorescence in situ hybridization (FISH) is increasingly used as an adjunct to conventional cytogenetic analysis in the diagnosis of haematological malignancies and in monitoring minimal residual disease. FISH, however, is generally performed on slides prepared after short-term sample incubation and therefore, whilst faster than conventional cytogenetics, still requires a minimum of 2 days for a result to be obtained. A simplification of the FISH procedure is reported using uncultured cytospin preparations of bone marrow or peripheral blood for the rapid diagnosis of the BCR-ABL and PML-RARa gene rearrangements. It demonstrates that culturing has no effect on the ratio of normal to abnormal cells in the nondividing population. Data is presented from an analysis of 24 cases in whom unequivocal results were obtained in less than 12 h and in complete concordance with results obtained by conventional cytogenetics and/or interphase FISH.
...
PMID:Rapid detection of BCR/ABL and PML/RARA using fluorescence in situ hybridization in cytospin preparations. 1079 99

In the prechemotherapy era arsenic derivatives were used for treatment of chronic myelogenous leukemia, a myeloproliferative disorder characterized by the t(9;22) translocation, the Philadelphia chromosome (Ph+). In acute promyelocytic leukemia response to arsenic trioxide (As2O3) has been shown to be genetically determined by the acute promyelocytic leukemia-specific t(15;17) translocation product PML/RARalpha. Hence, we reasoned that As2O3 might have a selective inhibitory effect on proliferation of BCR-ABL-expressing cells. Here, we report that: (a) As2O3 induced apoptosis in Ph+ but not in Ph- lymphoblasts; (b) enforced expression of BCR-ABL in U937 cells dramatically increased the sensitivity to As2O3; (c) the effect of As2O3 was independent of BCR-ABL kinase activity; and (d) As2O3 reduced proliferation of chronic myelogenous leukemia blasts but not of peripheral CD34+ progenitors. In summary, these data establish As2O3 as a tumor cell-specific agent, making its clinical application in Ph+ leukemia feasible.
...
PMID:BCR-ABL mediates arsenic trioxide-induced apoptosis independently of its aberrant kinase activity. 1091 48

Tetrasomy for the distal long arm of chromosome 15 is a rare finding. It has been previously described in seven patients, all of whom had a supernumerary marker chromosome (SMC) derived from distal 15q. These SMC contained no apparent centromeres (C-band/alpha-satellite negative), and belong to a novel class of SMC with neocentromeres. We present the oldest surviving patient with tetrasomy for distal 15q. The proposita was a 10-year-old girl with moderate to severe mental retardation, absent speech, hypotonia, minor facial anomalies, unusual digits, and pigmentation anomalies. Mosaicism for a symmetrical SMC was identified in metaphases from lymphocytes and fibroblasts. Parental karyotypes were normal, indicating a de novo origin for the SMC. FISH with a whole chromosome paint for chromosome 15 showed that the SMC was derived entirely from chromosome 15. However, C-banding and FISH with chromosome 15 probes D15Z1, D15S11, SNRPN, and PML were all negative. FISH with the FES probe at 15q26 showed hybridization to both ends of the SMC. The marker was interpreted as an analphoid inverted duplication of 15q25-->qter containing a presumed neocentromere. Previous molecular studies suggested either a mitotic or paternal meiotic origin for these distal 15q SMC. However, molecular analysis with chromosome 15 polymorphic markers showed that the analphoid SMC(15) in the proposita originated from a maternal meiotic error. The origins and mechanisms involved in formation of these distal 15q SMC appear to be more diverse than for the proximal pseudodicentic SMC(15).
...
PMID:Tetrasomy 15q25-->qter: cytogenetic and molecular characterization of an analphoid supernumerary marker chromosome. 1095 63

Interferon alpha (IFNalpha) has significant clinical activity in the treatment of patients with chronic myelogenous leukaemia (CML), but the mechanisms of its selective efficacy in the treatment of the disease are unknown. The CrkL adaptor protein interacts directly with the BCR-ABL fusion protein that causes the malignant transformation and is constitutively phosphorylated in BCR-ABL-expressing cells. In the present study, we provide evidence that CrkL was engaged in IFNalpha-signalling in the CML-derived KT-1 cell line, which expresses BCR-ABL and is sensitive to the growth inhibitory effects of IFNalpha. CrkL is constitutively associated with BCR-ABL in these cells and treatment with IFNalpha had no effect on the BCR-ABL/CrkL interaction. After IFNalpha stimulation, CrkL associated with Stat5, which also underwent phosphorylation in an IFNalpha-dependent manner. The interaction of CrkL with Stat5 was facilitated by the function of both the SH2 and the N-terminus SH3 domains of CrkL. The resulting CrkL-Stat5 complex translocated to the nucleus and could be detected in gel shift assays using elements derived from either the beta-casein promoter or the promoter of the PML gene, an IFNalpha-inducible gene that mediates growth inhibitory responses. In addition to its interaction with Stat5, CrkL interacts with C3G in KT-1 cells and such an interaction regulates the downstream activation of the small GTPase Rap1, which also mediates inhibition of cell proliferation. Thus, despite its engagement by BCR-ABL in CML-derived cells, CrkL mediates activation of downstream signalling pathways in response to the activated type I IFN receptor and such signals may contribute to the generation of the anti-proliferative effects of IFNalpha in CML.
...
PMID:Engagement of the CrkL adaptor in interferon alpha signalling in BCR-ABL-expressing cells. 1116 25

Qualitative RT-PCR methods used for monitoring minimal residual disease (MRD) in APL patients fail to predict relapse in up to 25% of patients in remission. We report here the development and evaluation of a highly sensitive (10(-5) and 10(-6) with one round and two rounds of PCR, respectively) competitive RT-PCR method to quantitate the PML-RARalpha fusion transcripts. PML-RARalpha transcript's levels were normalised to 10(5) copies of ABL transcript. Serial BM and PB samples from 16 patients with APL and t(15;17) were examined. Presentation samples from three patients (three BM, one PB) showed levels in the range of 0.7 x 10(6)-3.5 x 10(6) and 1.2 x 10(5) molecules in BM and PB samples respectively. Serial quantitation of MRD in both BM and PB samples showed significantly lower levels of PML-RARalpha transcripts in remission, although the majority of samples remain positive for the PML-RARalpha transcripts even those in long-term remission (up to 94 months). Levels of PML-RARalpha in remission samples were up to 2 x 10(2) and up to 5.2 x 10(1) molecules in BM and PB respectively. BM and PB samples taken from two patients 2-4 months before relapse showed significantly higher levels of PML-RARalpha transcripts (1.2 x 10(4) molecules in BM; 3.5 x 102, 1.2 x 10(2) and 1.2 x 10(3) in PB). The same samples, when tested with a standard qualitative RT-PCR for the amplification of PML-RARalpha (with a sensitivity of 10(-4)) produced negative results. This indicates that the qualitative methods would not have predicted relapse in these patients. Our data show that quantitating PML-RARalpha transcripts with a sensitive method may provide a superior approach for monitoring MRD in APL and identifying patients at high risk of relapse.
...
PMID:Monitoring minimal residual disease and predicting relapse in APL by quantitating PML-RARalpha transcripts with a sensitive competitive RT-PCR method. 1145 74


1 2 3 4 5 6 7 Next >>

---