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)

An Ohmeda Biox 3700 oximeter was evaluated during treatment of 12 patients with respiratory distress. The infants were of 27-33 weeks' gestation and between 2 days and 5 months postnatal age. Blood gases were taken from indwelling arterial catheters and were measured on an ABL 30 blood gas analyser. The study tested the accuracy of the oximeter in detecting hypoxia (PaO2 less than 55 mmHg) and hyperoxia (PaO2 greater than 80 mmHg). Results are based on 175 paired observations. Guidelines are suggested for the use of the pulse oximeter under three conditions. In a newborn infant with acute respiratory distress without direct arterial access, the limits should be set at 85% (lower) and 90% (upper). In an older infant with chronic respiratory distress, the upper limit of use should be 95%. In order to avoid oxygen tensions less than 55 mmHg which would increase the risk of pulmonary vasoconstriction, however, the lower limit should be 87%. Infants with indwelling arterial lines during their first few weeks of treatment should have oxygen tension measurements and simultaneous oxygen saturation readings plotted on a graph at the bedside. The graph should be updated every 48 h to take into account changed levels of 2,3-diphosphoglycerate, haemoglobin F, and carboxyhaemoglobin and the recommended limits should be changed accordingly.
Aust Paediatr J 1988 Dec
PMID:Guidelines for the use of pulse oximetry in the non-invasive estimation of oxygen saturation in oxygen-dependent newborn infants. 314 63

An improved two-step clean up procedure involving alumina-silica column chromatography and gel permeation chromatography (GPC) of air particulate matter (NBS SRM 1648) and river sediment extracts and a GPC clean up procedure for marine biota samples are described for the determination of polycyclic aromatic hydrocarbons with two to five rings and selected polychlorinated biphenyl congeners, respectively. Bio-Beads SX-12 and SX-3 were used as packing materials. The recoveries obtained varied from 52 to 78% depending on the compound. Quantitative data for NBS SRM 1648 were comparable with those described previously for this sample.
J Chromatogr 1988 Dec 02
PMID:Selective enrichment procedures for the determination of polychlorinated biphenyls and polycyclic aromatic hydrocarbons in environmental samples by gel permeation chromatography. 314 50

A great deal of information has emerged over the past decade regarding the gene structures and corresponding protein products of the cellular and transformation-associated forms of the ABL tyrosine kinase family. Many reports have also detailed the biological effects of these proteins (particularly the viral ABL forms) on a broad range of cell types. However, in spite of all these research efforts, the precise role of the ABL gene in normal and neoplastic growth remains to be determined. To elucidate the mechanism of action of normal and altered ABL proteins, it is imperative to identify their relevant cellular substrates and establish the role of the ABL target proteins in transformation and normal cellular growth. The availability of temperature-sensitive ABL proteins, coupled with the use of sensitive anti-phosphotyrosine antibodies, should be useful in this respect. Purification of enzymatically active, intact forms of the ABL proteins produced in insect cells by employing baculovirus expression vectors should permit direct comparison of the biochemical properties and tertiary structures of the various members of the ABL protein kinase family. Such studies will aid in understanding the nature of the alteration of ABL which results in the activation of its transforming potential. Furthermore, the availability of purified ABL proteins should permit examination of interactions of ABL with other growth-regulatory proteins, such as growth factor receptors. It has been shown that transformation-associated ABL proteins interact with the IL-3, IL-2 and GM-CSF growth-factor pathways. These and other components of the cellular signalling pathways are potential ABL targets. The elucidation of ABL function by a variety of approaches such as those described above will ultimately aid in the development of far-reaching therapeutic treatments for at least two forms of human leukaemia: Ph positive CML and Ph positive ALL.
Baillieres Clin Haematol 1987 Dec
PMID:Role of the ABL oncogene tyrosine kinase activity in human leukaemia. 333 51

The Ph chromosome is the hallmark of CML, where it is found in more than 90% of the cases. Cytogenetically, it usually results from a t(9;22)(q34;q11). The Ph arises in a stem cell and in chronic phase is found in all haematopoietic cell lineages, although it causes only increased granulopoiesis, and sometimes increased thrombopoiesis; furthermore blast crisis may occur in all differentiative patterns of the pluripotent stem cell. Recently, molecular investigations of Ph positive CML cases have revealed a consistent genomic recombination between two genes, BCR on chromosome 22 and the ABL oncogene. The latter is translocated from 9q34, its normal site, to the 22q- or Ph chromosome. This molecular rearrangement expresses a unique 8.5 kb BCR-ABL hybrid mRNA transcript, that encodes an altered BCR-ABL protein of approximately 210 kD with enhanced in vitro tyrosine kinase activity. The breakpoints on chromosome 22q- are clustered in a 5 kb DNA fragment, allowing their study using Southern blot analysis. Cytogenetic variant forms of the Ph translocation involving three or more chromosomes are found in about 5% of the cases. Southern blot and in situ hybridization studies have demonstrated that these variants are cytogenetically more complex than the standard t(9;22) but molecularly they show the same essential genomic recombination. This is also true for a small number of cases of Ph negative CML. Clonal progression, indicated by the presence of clonal, non-random chromosome abnormalities, in addition to the Ph is rare during chronic phase but is found in 80% of blast crisis. These additional aberrations may precede BC by weeks or months and have therefore a clear prognostic value. Ph is not restricted to CML, since it is also found in ALL (20% of adult cases) and rarely in AML. Ph in acute leukaemia is cytogenetically indistinguishable from Ph in CML, but molecular studies have shown that in 50% of the cases the breakpoint on chromosome 22 is different from the very consistent and characteristic breakpoint in CML. Nevertheless genomic recombination takes place that results in a novel ABL protein at least in some of the cases. Despite extensive cytogenetic and molecular investigations, the mechanisms underlying the formation of the Ph as well as the pathogenesis of Ph positive CML are still unknown but are now the object of intensive research.
Baillieres Clin Haematol 1987 Dec
PMID:Chromosome abnormalities in CML. 333 58

A DNA region on chromosome 22, designated M-BCR, contains the chromosomal breakpoint of the Philadelphia (Ph) translocation in all Ph positive CML patients studied to date. M-BCR is part of a gene, BCR, oriented with its 5' end towards the centromere of chromosome 22. All of the CML DNAs analysed have a breakpoint within introns of the BCR gene. As a consequence of the Ph translocation the 3' end of the BCR gene has been translocated to chromosome 9, while the 5' part remains on the Ph chromosome. The remaining BCR sequences act as an acceptor for a chromosome 9 gene, the ABL oncogene: the ABL oncogene is fused in a head-to-tail fashion to the chromosome 22 sequences. This genomic configuration results in the transcription of a novel chimeric mRNA consisting of 5' BCR sequences and 3' ABL oncogene sequences. In K562, a cell line derived from a CML patient, and in five CML patients such chimeric BCR/ABL transcripts have been demonstrated. An abnormally sized ABL protein has been detected in the cell line K562 and in leukaemic cells from patients. This protein represents the translational product of the chimeric mRNA. The role of the BCR part of the fusion protein is unknown; it is possible that the BCR moiety could alter the structure of the ABL protein and unmask its tyrosine kinase activity. By analogy with the gag/v-abl polyprotein, the CML-specific BCR/ABL protein might have transforming activity and could play an essential role in the generation and/or maintenance of CML.
Baillieres Clin Haematol 1987 Dec
PMID:The BCR/ABL hybrid gene. 333 59

The mechanism(s) with which tumor target cells actively resist the lethal lesion induced by murine macrophage cytolytic factory (CF) has been probed by drug-induced sensitization of these cells. We have examined whether drug-induced sensitization is attributable to the action of these drugs on cellular DNA, RNA, or protein synthetic rates. The murine mammary adenocarcinoma cell line EMT-6 pretreated with a dose range of actinomycin-D (.03-3.0 micrograms/ml) for 4 hr was inhibited from 66 to 98% in DNA synthesis rate, from 81 to 93% in RNA synthesis rate, and from 38 to 52% in protein synthesis rate. The maximum sensitization toward lysis by CF was achieved with a drug dose of 1.0 micrograms/ml. The lack of correlation between the drug-induced effects on sensitization and effects on these metabolic rates was evident from the correlation coefficients for the percentage of maximum sensitization of the target toward CF-induced lysis, and the percent of inhibition of DNA, RNA, and protein synthesis. These were 0.11, -0.11, -0.44, respectively. Similarly, target cells treated with a dose range of cycloheximide (0.3-30 micrograms/ml) were inhibited from 81 to 95% in DNA synthesis rate, 68 to 81% in RNA synthesis rate, and 82 to 93% in protein synthesis rate. However, at none of the drug levels employed was significant sensitization of the target cell to CF-induced lysis observed. This was reflected in the correlation coefficients of -0.55, -0.28, and -0.34 for DNA, RNA, and protein synthetic rates, respectively. The essential role of cellular microtubule-dependent events early in the lytic mechanism was demonstrated by exposing colchicone-treated targets to CF. While colchicone could markedly inhibit lysis if introduced before CF, this inhibitory effect was not detected if the drug were withheld for 4 hr after CF exposure. The importance of the repair mechanism(s) early in the cellular response to lesion formation was demonstrated by altering the schedule for CF and actinomycin D administration to the target. If actinomycin D treatment was withheld from the targets for as little as 3 hr following introduction of CF, the lytic mechanism had already bypassed the drug-sensitive steps, manifest in markedly decreased susceptibility to lysis. Collectively, the data show that the ability of the EMT-6 target cells to resist CF-induced lysis does not depend solely on the ability of the cells to synthesize DNA, RNA, or protein.
J Leukoc Biol 1986 Dec
PMID:Sensitization of tumor target cells to cytolysis by murine macrophage cytolytic factor by drugs inhibiting DNA, RNA, and protein synthesis. 346 37

Immunologists working in the field of autoimmunity tend to concentrate all their efforts on the elucidation of possible malfunctions of the immune system, particularly pathologic changes of immune regulation. Also in the OS model various groups of investigators emphasized this approach, although it was already clear early in the history of this model that SAT has a multigenic background. The fact that this disease cannot be transferred into normal, histocompatible animals without an appropriate non-MHC linked genetic background was a strong indication that detailed studies of thyroid-associated factors may be warranted for the elucidation of the pathogenesis of this disease and perhaps also its human counterpart, Hashimoto thyroiditis. Since several reviews on the immunologic aspects in the OS model have been published in recent years we have in this communication attempted to discuss the - mostly still rudimentary - findings concerning the target organ itself, including morphological changes before the beginning of infiltration, the analysis of Tg, the altered thyroid function before onset of SAT, the results of cross-breeding studies of OS and inbred normal chickens in respect to the susceptibility of the offspring for the transfer of SAT, the possible role of a virus infection and the aberrant expression of MHC class II antigens on TEC. Cross-breeding studies revealed that most probably a single gene is responsible for the primary altered thyroid function and at least 3 genes code for the susceptibility of the OS thyroid gland to the autoimmune attack. It is not yet clear for which of the above-mentioned observations each of these genes is responsible and what is/are the initial triggering mechanism(s). Ongoing studies in our laboratory concentrate on this question, specifically the potential role of endogenous viruses in this process.
Immunol Rev 1986 Dec
PMID:The role of genetically-determined primary alterations of the target organ in the development of spontaneous autoimmune thyroiditis in obese strain (OS) chickens. 346 60

The Philadelphia chromosome, observed in greater than 90% of patients with chronic myelogenous leukemia, results from a reciprocal translocation between chromosomes 9 and 22. The translocation breakpoint on chromosome 9 occurs near the ABL gene and correlates with the production of a chronic myelogenous leukemia-specific 8.5-kilobase ABL-related mRNA species accompanied by a structurally altered ABL protein (P210c-abl). The N-terminal sequence of the protein is derived from the BCR gene on chromosome 22. We have isolated overlapping cDNA clones from the K-562 cell line corresponding to approximately 8.5 kilobases of mRNA and have sequenced 2550 nucleotides at the 5' end. Our results indicate that the 5' end of the 8.5-kilobase mRNA consists of greater than 400 nucleotides of noncoding sequence that are greater than 80% G + C rich. Based on our sequence analysis, we propose that initiation of translation occurs at nucleotide 471, such that the initial 927 amino acids of P210c-abl are derived from BCR sequences. Our cDNA clones thus define the complete coding sequences for the P210c-abl gene product.
Proc Natl Acad Sci U S A 1986 Dec
PMID:Overlapping cDNA clones define the complete coding region for the P210c-abl gene product associated with chronic myelogenous leukemia cells containing the Philadelphia chromosome. 354 Sep 51

An assay using a bimane derivative has been developed to detect free glutathione (GSH) in individual viable cells by flow cytometry. Monochlorobimane [syn-(ClCH2CH3)-1,5-diazabicycla[3.30]acta-3,6-diene-2,8-dio ne], itself nonfluorescent, reacts with GSH to form a highly fluorescent derivative. High pressure liquid chromatography analysis showed that, using specific staining conditions, the only low molecular weight fluorescent derivative formed in Chinese hamster ovary cells was that formed with GSH. Very little reaction with protein sulfhydryls was observed. Rates of GSH depletion in Chinese hamster ovary cells exposed to diethylmaleate were essentially the same, whether measured by relative fluorescence intensity, by flow cytometry or by enzymatic assay on cellular extracts. This method was shown to be useful for measurement of GSH resynthesis, uptake, and depletion by prolonged hypoxia and misonidazole treatment. Since measurements are made on individual cells, cell-to-cell variation and populational heterogeneity in GSH content are revealed by flow cytometry. Although under most conditions in vitro GSH content is relatively homogeneous, under certain circumstances, such as release from hypoxia, heterogeneity in populational GSH levels was observed. The significance of this heterogeneity is discussed in regard to the induction of gene amplification and drug resistance by transient hypoxia. Numerous subclones of Chinese hamster ovary cells selected by growth in Adriamycin or methotrexate-containing medium express elevated levels of GSH per cell. The method was extended to quantitate the GSH content of cells excised from EMT-6/SF mouse tumors that had been treated in vivo with L-buthionine-S-R-sulfoximine, an inhibitor of GSH synthesis. The bivariate analysis (forward angle light scatter versus monochlorobimane fluorescence) of cells derived from these tumors gave excellent resolution of normal and tumor cells and demonstrated extensive heterogeneity in the tumor cell population with respect to GSH content per cell.
Cancer Res 1986 Dec
PMID:Quantitative analysis of cellular glutathione by flow cytometry utilizing monochlorobimane: some applications to radiation and drug resistance in vitro and in vivo. 377 30

The outcome from cardiopulmonary arrest in children in the prehospital and hospital setting is generally poor. The event that compromises the cardiac status is often respiratory embarrassment, and the presenting rhythms are often bradyarrhythmias and asystole. Emergency medical services (EMS) systems have primarily an adult focus and may not be organized to manage optimally the critically ill and injured child. Data from a survey of training programs demonstrate that paramedic and EMT education in pediatric emergencies may be inadequate. Forty-one percent of the programs surveyed had less than 10 hr of pediatric training. Data suggest that EMS providers may not be equipped to manage children effectively. The Los Angeles EMS System for children is described. There are two levels of receiving facilities: Emergency Departments Approved for Pediatrics and Pediatric Critical Care Centers. The system is voluntary and has 85% of the hospitals in compliance with the guidelines. Early recognition of the prearrest state, improved training, and equipping of prehospital care personnel, development of EMS services for children, dissemination of an advanced pediatric life support course, as well as research in pediatric CPR may improve the outcome of resuscitation in the pediatric population.
Circulation 1986 Dec
PMID:A needs assessment of advanced life support and emergency medical services in the pediatric patient: state of the art. 377 27


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