Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.10.2 (focal adhesion kinase)
 44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Many medical schools have required emergency medicine courses for freshmen medical students, usually through participation in BLS (basic life support) or EMT activities. For several years students at our institution have participated in a required emergency medical technician-ambulance grade (EMT-A) course. While retaining much of the material presented in that original EMT-A course, the course has now been expanded to serve as the medical students' introduction to clinical medicine. This expansion resulted from the belief that emergency medicine provides initial patient contact in the presence of a faculty uniquely suited to introduce the broad domain of clinical medicine to the medical student. Emergency physicians, more than any other specialists, must possess the ability to obtain an incisive history promptly, perform an accurate physical examination, and arrive at an assessment with limited laboratory and radiologic data. Initial access to the clinical education of medical students provides the opportunity to direct their efforts in a prioritized fashion, and thus helps to organize their thought processes for further development as clinicians. Departments of emergency medicine should be willing to accept this incremental responsibility for the introduction of the medical student to the clinical and laboratory assessment of patients.
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PMID:Expansion of emergency medicine's responsibilities for preclinical education of medical students. 397 Mar 98

By the principle of identity by descent, parental consanguinity in individuals with rare recessively transmitted disorders dictates homozygosity not just at the mutated disease-associated locus but also at sequences that flank that locus closely. In 25 of 26 individuals with Bloom syndrome examined whose parents were related, a polymorphic tetranucleotide repeat in an intron of the protooncogene FES was homozygous, far more often than expected (P < 0.0001 by chi 2). Therefore, BLM, the gene that when mutated gives rise to Bloom syndrome, is tightly linked to FES, a gene whose chromosome position is known to be 15q26.1. This successful approach to the assignment of the Bloom syndrome locus to one short segment of the human genome simultaneously (i) demonstrates the power of homozygosity mapping and (ii) becomes the first step in a "reverse" genetics definition of the primary defect in Bloom syndrome.
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PMID:Bloom syndrome: an analysis of consanguineous families assigns the locus mutated to chromosome band 15q26.1. 802 33

Bloom syndrome (BS) is more common in the Ashkenazi Jewish than in any other population. Approximately 1 in 110 Ashkenazi Jews carries blm, the BS mutation. The locus mutated in BS, BLM, maps to chromosome subband 15q26.1, tightly linked to the proto-oncogene FES. We have investigated the basis for the increased frequency of blm in the Ashkenazim by genotyping polymorphic microsatellite loci tightly linked to BLM in affected and unaffected individuals from Ashkenazi Jewish and non-Ashkenazi populations. A striking association of the C3 allele at FES with blm (delta = .422; p = 5.52 x 10(-7)) and of the 145-bp and 147-bp alleles at D15S127 with blm (delta = .392 and delta = .483, respectively; p = 2.8 x 10(-5) and p = 5.4 x 10(-7), respectively) was detected in Ashkenazi Jews with BS. This linkage disequilibrium constitutes strong support for a founder-effect hypothesis: the chromosome in the hypothetical founder who carried blm also carried the C3 allele at FES and either the 145-bp or the 147-bp allele at D15S127.
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PMID:Linkage disequilibrium between the FES, D15S127, and BLM loci in Ashkenazi Jews with Bloom syndrome. 807 89

Mutation of the Bloom's syndrome (BS) gene, BLM, results in genomic instability. As the first step toward positional cloning of the gene, tight linkage of BLM and FES at 15q26.1 was detected by genotyping affected in families in which the parents are cousins, so-called homozygosity mapping. Linkage disequilibrium between BLM and FES was detected in Ashkenazi Jews with BS, confirming the linkage results and supporting the hypothesis that the increased frequency of the BS mutation in the Ashkenazim is due to founder effect. The mutated BLM gene is inherited identical by descent in BS persons whose parents are cousins or Ashkenazi Jewish; in persons whose parents do not share a common ancestor, BLM can be mutant at different positions within the gene. In such persons, crossing-over within BLM can occur to form a functionally wild-type gene capable of correcting the mutant phenotype of BS cells. In half the cases in which such somatic intragenic recombination had occurred, reduction to homozygosity was detectable distal to BLM but not proximal to it. We localized the cross-over points in corrected cells to a 250 kb genomic segment and isolated therefrom a 4437 bp cDNA that encodes a 1417 amino acid protein homologous to the RecQ subfamily of DExH box-containing DNA and RNA helicases. The identification of BLM as a putative DNA helicase provides a new and powerful tool to investigate the primary defect in BS and the function of the BLM gene product in maintaining the integrity of the genome.
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PMID:Molecular genetics of Bloom's syndrome. 887 52

This paper presents an experience of the Educational Centre of EMSC Sarajevo in the postgraduate training of the various profiles of medical personnel (medical doctors and medical technicians) that are employed in the emergency services of the pre-hospital and hospital type in Bosnia and Herzegovina. A period of the last four years (1996-2000) when the Educational Centre was restructured, becoming a one of the most active services in the medical sector of the EMSC Sarajevo has been emphasised in particular. Educational Centre of EMSC was participating in a number of international projects related to the education. Forty-five (45) courses of the various levels and with different programs: BLS, ALS, ACLS, ACLS-instructor course, ATLS, EMT-course, EMT-advanced, EMT-instructor and EMT-dispatcher course were carried out in the mentioned period. Seven thousand eight hundred and twelve (7812) hours of theoretical teaching and practical training were provided for the 570 candidates who successfully completed training in various programs. First aid training for civilian population was also conducted. Twenty one first.aid courses were carried out and successfully achieved by 324 candidates. On this way, 196 hours of theoretical teaching and practical training were realised. In order to make first aid training popular, 160 children from pre-school institutions (kindergartens) of Sarajevo Canton were also introduced to first aid principles. It has been pointed out that well equipped and trained team for the urgent medical intervention with a necessary team work is a crucial factor for the successful treatment of emergency that means a patient in life threatening situation.
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PMID:[Development and organization of the Education Center at the Institute of Emergency Medical Services in Sarajevo]. 1111 30

Sliding clamps tether DNA polymerases to DNA to increase the processivity of synthesis. The Escherichia coli gamma complex loads the beta sliding clamp onto DNA in an ATP-dependent reaction in which ATP binding and hydrolysis modulate the affinity of the gamma complex for beta and DNA. This is the second of two reports (Williams, C. R., Snyder, A. K., Kuzmic, P., O'Donnell, M., and Bloom, L. B. (2004) J. Biol. Chem. 279, 4376-4385) addressing the question of how ATP binding and hydrolysis regulate specific interactions with DNA and beta. Mutations were made to an Arg residue in a conserved SRC motif in the delta' and gamma subunits that interacts with the ATP site of the neighboring gamma subunit. Mutation of the delta' subunit reduced the ATP-dependent beta binding activity, whereas mutation of the gamma subunits reduced the DNA binding activity of the gamma complex. The gamma complex containing the delta' mutation gave a pre-steady-state burst of ATP hydrolysis, but at a reduced rate and amplitude relative to the wild-type gamma complex. A pre-steady-state burst of ATP hydrolysis was not observed for the complex containing the gamma mutations, consistent with the reduced DNA binding activity of this complex. The differential effects of these mutations suggest that ATP binding at the gamma1 site may be coupled to conformational changes that largely modulate interactions with beta, whereas ATP binding at the gamma2 and/or gamma3 site may be coupled to conformational changes that have a major role in interactions with DNA. Additionally, these results show that the "arginine fingers" play a structural role in facilitating the formation of a conformation that has high affinity for beta and DNA.
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PMID:Mechanism of loading the Escherichia coli DNA polymerase III sliding clamp: II. Uncoupling the beta and DNA binding activities of the gamma complex. 1461 68

This case study represented a patient with a relatively uncomplicated myocardial infarction that, after prompt prehospital care and transport, was successfully halted in the emergency department with fibrinolytic therapy. This patient was provided excellent care in the prehospital setting because the paramedic and his EMT-B partner worked together effectively as a team. Although ECG monitoring, IV therapy and medication administration are beyond the usual scope of practice of an EMTB, many EMS systems are training their EMT-Bs to assist with these important procedures and interventions. This involves preparing IV equipment and supplies, applying the cardiac monitor, and recognizing and handling the various paramedic medications. This enhanced role of the EMT-B allows the paramedic to perform a more focused and careful patient assessment. A cohesive working relationship between BLS and ALS personnel is absolutely crucial to the outcome of the patient. Although each level of prehospital provider possesses a different knowledge of pathophysiology and patient management, it is the combined contributions and efforts of each provider that will afford patients the high quality of care they deserve.
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PMID:Cardiac case study. 50-year-old male with chest pressure. 1627 74

Altered signaling pathways are key regulators of cellular functions in tumor cells. Constitutive activation of signal transducer and activator of transcription (STAT)3 and -5 may be involved in tumor formation and progression. We have investigated the role of STAT5 in cutaneous melanoma metastases using various RNA and protein techniques. In melanoma specimens, Stat5b transcripts were upregulated approximately 3.8-fold. In 13 of 21 (62%) human melanoma metastases, STAT5 was phosphorylated in comparison to normal human melanocytes and benign nevi. The STAT5 target gene Bcl-2 was frequently upregulated. The investigation of the underlying mechanism revealed specific STAT5 activation by recombinant human epidermal growth factor (rEGF). rEGF-induced activation of STAT5 occurred in vitro through the non-receptor tyrosine kinases transforming gene (src) of Rous Sarcoma virus and Janus kinase 1. Inhibition of Stat5b expression by small interfering RNA strongly reduced the expression of Bcl-2 and led to decreased cell viability and increased apoptosis in the melanoma cell lines A375 and BLM. Transfection with dominant-negative Stat5b caused enhanced cell death and G1 arrest in A375 cells. Our study identifies phosphorylated STAT5 in melanoma and shows regulation through rEGF; STAT5 may thus act as a survival factor for growth of human melanoma and may represent a potential target for molecular therapy.
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PMID:STAT5 phosphorylation in malignant melanoma is important for survival and is mediated through SRC and JAK1 kinases. 1674 10

4-Hydroxy-2-nonenal (4-HNE), one of the major biologically active aldehydes formed during inflammation and oxidative stress, has been implicated in a number of cardiovascular and pulmonary disorders. 4-HNE has been shown to increase vascular endothelial permeability; however, the underlying mechanisms are unclear. Hence, in the current study, we tested our hypothesis that 4-HNE-induced changes in cellular thiol redox status may contribute to modulation of cell signaling pathways that lead to endothelial barrier dysfunction. Exposure of bovine lung microvascular endothelial cells (BLMVECs) to 4-HNE induced reactive oxygen species generation, depleted intracellular glutathione, and altered cell-cell adhesion as measured by transendothelial electrical resistance. Pretreatment of BLM-VECs with thiol protectants, N-acetylcysteine and mercaptopropionyl glycine, attenuated 4-HNE-induced decrease in transendothelial electrical resistance, reactive oxygen species generation, Michael protein adduct formation, protein tyrosine phosphorylation, activation of ERK, JNK, and p38 MAPK, and actin cytoskeletal rearrangement. Treatment of BLMVECs with 4-HNE resulted in the redistribution of FAK, paxillin, VE-cadherin, beta-catenin, and ZO-1, and intercellular gap formation. Western blot analyses confirmed the formation of 4-HNE-derived Michael adducts with the focal adhesion and adherens junction proteins. Also, 4-HNE decreased tyrosine phosphorylation of FAK without affecting total cellular FAK contents, suggesting the modification of integrins, which are natural FAK receptors. 4-HNE caused a decrease in the surface integrin in a time-dependent manner without altering total alpha5 and beta3 integrins. These results, for the first time, revealed that 4-HNE in redox-dependent fashion affected endothelial cell permeability by modulating cell-cell adhesion through focal adhesion, adherens, and tight junction proteins as well as integrin signal transduction that may lead dramatic alteration in endothelial cell barrier dysfunction during heart infarction, brain stroke, and lung diseases.
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PMID:Redox regulation of 4-hydroxy-2-nonenal-mediated endothelial barrier dysfunction by focal adhesion, adherens, and tight junction proteins. 1698 27

As an EMT-B, there will be times when your assessment and treatment skills will be put to the test as you find yourself on scene with a critical patient and no ALS backup. Your ability to recognize patients with critical symptoms and do the most good for them within the EMT-B scope of practice could have a tremendous impact on patient survival. The importance of rapid but accurate assessment of both the clinical presentation and the patient's history cannot be overemphasized. This article will review BLS assessment and care of the congestive heart failure (CHF) patient.
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PMID:Skills review: the CHF patient. A review of BLS ssessment and care of the congestive heart failure patient. 1971 72


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