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)

The effect of the substituted benzaldehyde BW12C on haemoglobin-oxygen binding affinity, tumour radiation response and blood perfusion were investigated in a C3H mouse mammary carcinoma grown in the feet of CDF1 mice. Mouse P50 (partial pressure of oxygen at half saturation) was estimated using an ABL blood gas analyzer; radiation response determined from tumour regrowth and local tumour control assays; and tumour blood perfusion measured with a 86RbCl extraction procedure. A single intravenous injection of BW12C substantially decreased mouse P50. This effect was dependent on the time after injection with the nadir observed within 15 min and only returning to normal after several hours. It was also dependent on drug dose, the decrease becoming larger with increasing concentration, reaching a maximum 50% reduction at 70 mg/kg. The decrease in P50 could be maintained for at least 6 h following injection of 70 mg/kg, if mice were also given 25 mg/kg at hourly intervals. However, no changes in radiation response or tumour blood perfusion were observed with either single or multiple administrations of BW12C. These results suggest that BW12C induced changes in tumour hypoxia reported by several groups of workers, may not be entirely the result of a change in haemoglobin-oxygen affinity.
Radiother Oncol 1992 Sep
PMID:BW12C-induced changes in haemoglobin-oxygen affinity in mice and its influence on the radiation response of a C3H mouse mammary carcinoma. 141 May 89

Recently we described the establishment in culture and the immunophenotypic and functional characteristics of a human T-leukemia line TALL-103/2 derived from the T-cell receptor (TCR)-gamma/delta subset of T-lymphocytes. TALL-103/2 cells are absolutely dependent on interleukin 2 (IL-2) for their growth and survival in culture and thus provide a model cell line for studies of IL-2 signal transduction in a TCR-gamma/delta T-cell. In this report, we focus on the regulation of SRC-family protein tyrosine kinases (PTKs) by IL-2. TALL-103/2 cells were found to contain p56-LCK, p59-FYN, p62-YES and p53/56-LYN. Stimulation of growth factor-deprived TALL-103/2 cells with IL-2, however, induced increases in the relative activity only of the p56-LCK kinase. This IL-2-mediated increase in LCK kinase activity was manifested both by increased kinase autophosphorylation and by increased phosphorylation of the exogenous substrate enolase during in vitro kinase assays. Furthermore, immunoblot assays determined that the levels of p56-LCK protein were unaltered by IL-2-treatment, indicating that the measured elevations in LCK kinase activity reflected an increase in the specific activity of this PTK. In TALL-103/2 cells, IL-2 stimulated concentration-dependent increases in p56-LCK activity that displayed rapid and transient kinetics: detectable increases occurred within 1 minute after IL-2 stimulation, peaked at 10 minutes, and declined to baseline levels by 30 minutes. Treatment of TALL-103/2 cells with IL-4 abrogated IL-2-initiated proliferation, but did not inhibit IL-2-mediated activation of p56-LCK.(ABSTRACT TRUNCATED AT 250 WORDS)
Cytokine 1992 Sep
PMID:Interleukin 4 inhibits IL-2-induced proliferation of a human T-leukemia cell line without interfering with p56-LCK kinase activation. 142 Sep 98

Candida spp. is frequently detected from perioperative patients, especially from those requiring central venous catheter (CVC) management. CAND-TEC could detect the blood fungus infection easily and quickly. We analyzed 438 specimens from 57 patients requiring perioperative CVC management for more than three weeks, and investigated usefulness of CAND-TEC comparing with other serological methods. The dilution rate of CAND-TEC showed a positive correlation with amount of beta-D-glucan which was measured by Toxicolor test and Endotoxin-specific assay. It also showed a positive correlation with amount of D-arabinitol. When blood samples diluted more than four times were positive with CAND-TEC, the patients were considered to be infected, and accumulative infection rate was up to 84.2% three weeks after introduction of CVC management. CAND-TEC would be useful in detecting Candida infection compared with conventional methods, and the fungus infection was much more frequent incidence than ever expected. It is important to detect fungus infection early and respond immediately to avoid nosocomial infection.
Nihon Geka Gakkai Zasshi 1992 Sep
PMID:[Early diagnosis and management against perioperative fungus infection]. 147 Jan 56

200 sera stored after collection in 1988-1990 in Maharashtra state, India, were tested for HIV-1 and HIV-2 with standard kits. The sera were from diverse groups including prostitutes, blood donors, STD patients, foreigners, and renal transplant patients. The tests were recombinant HIV-1 and HIV-2 EIA (Abbott), Vironostika HIV mixt (Organon Teknika, Holland) and Genie HIV-1/HIV-2 rapid EIA (Genetic Systems, USA). Those testing positive were confirmed by an immunoblot test capable of distinguishing HIV-2 from HIV-1, LiaTeK HIV-1+2 Line immunoassay (Organon Teknika, Holland). 128 sera were positive for HIV-1 by Western Blot, and 40 that were positive for ELISA but negative by Western Blot. There were 14 sera positive for HIV-2, and 14 positive for both HIV-1 and HIV-2. 14 sera that were originally indeterminate, now tested positive for HIV-2. It was recommended that all sera in Maharashtra state indeterminate for HIV-1 by Western Blot be re-tested for HIV-2.
Indian J Med Res 1992 Sep
PMID:HIV-2 antibodies in serum samples from Maharashtra state. 147 22

When used for eyes with greater than average axial length (AXL), the SRK formula has been reported to have a tendency to yield more myopic refractions than those predicted. To further evaluate such findings, we studied 609 eyes with AXLs between 24.5 and 27.0 mm. Comparing the predicted with the actual refractions and calculating the range of errors, we found that the postoperative refractions were more myopic than predicted. Then, based on our evaluation of the relationship between the postoperative refractions and the powers of the implanted intraocular lenses (IOLs), we devised the following formula: R = 0.8 x (P - I) + 0.57 (P < .01) in which R = the postoperative refraction; P = the emmetropic IOL power; and I = the actual IOL power. Testing this modified SRK formula in 55 additional eyes, we found that the predicted postoperative refractions it yielded were more accurate than those calculated using five earlier formulas.
Ophthalmic Surg 1992 Sep
PMID:Modified SRK formula for axial myopia (24.5 mm < or = axial length < 27.0 mm). 148 Mar 68

The Philadelphia chromosome (Ph1) was the first genetic change to be associated consistently with leukemia, and it is one of the best understood on the molecular level. Because of this, it is an excellent model to investigate the application of molecular techniques to the clinical setting. These techniques are reviewed as are their clinical use in chronic myelogenous leukemia (CML), acute lymphoblastic leukemia (ALL), and transplantation. The Ph1 is caused by the fusion of two genes on chromosomes 9 and 22, resulting in the BCR-ABL fusion gene. This new gene is believed to be the cause of these Ph1-positive leukemias. The ability to detect the BCR-ABL fusion gene evolved from cytogenetic detection to Southern blot analysis, and now includes sophisticated techniques such as polymerase chain reaction (PCR) methods and pulsed-field gels. Diagnosis of the BCR-ABL fusion gene by Southern blot detection of bcr genetic rearrangements is the prototype of molecular cancer diagnosis. The sensitivity and clinical uses of this test are reviewed, especially its application to monitoring the response to treatment. PCR methods enable the researcher to detect 1 CML cell in a population of 10(5) cells. Clinical experience with PCR, especially in transplantation medicine, is providing a better understanding of the meaning of the terms "remission" and "cure." Newer techniques using fluorescent in situ hybridization have considerable potential for BCR-ABL detection, but no clinical experience has been gained with these techniques currently. The diagnosis of the BCR-ABL fusion gene in ALL has important clinical implications because it is the most common molecular genetic change in adult ALL and is associated with short remissions and poor outcome in all age groups. Diagnosis of the BCR-ABL fusion in ALL is difficult because the molecular findings are more heterogeneous than they are in CML. The methods available and their accuracy and sensitivity are compared. A review of their clinical impact is included.
Cancer 1992 Sep 15
PMID:The role of molecular techniques in the clinical management of leukemia. Lessons from the Philadelphia chromosome. 151 23

Twenty six patients with Philadelphia chromosome (Ph1) positive chronic myelogenous leukemia (CML) treated with IFN-alpha were classified on the basis of the fusion pattern of BCR/ABL chimeric mRNA determined by a reverse-transcriptase-polymerase chain reaction (RT-PCR) method. The relationship between the fusion pattern of BCR/ABL mRNA and the clinical outcome was also analysed. Twelve patients showed M-bcr exon 3/ABL exon 2 (B3/A2) chimeric mRNA and nine had M-bcr exon 2/ABL exon 2 (B2/A2) mRNA. Eleven of the 12 patients with B3/A2 achieved complete hematological response with IFN-alpha therapy, as did three of the nine patients with B2/A2. The mean duration to blastic crisis was significantly longer in the B3/A2 patients (mean 52.4 months) than in the B2/A2 patients (mean 26.2 months) (p less than 0.01). These results suggest that the fusion pattern of BCR/ABL mRNA may affect the therapeutic response to IFN-alpha and clinical outcome in CML patients.
Leukemia 1992 Sep
PMID:Possible correlation between fusion pattern of BCR/ABL mRNA and clinical response to alpha-interferon in chronic myelogenous leukemia. 151 6

The presence of calcitonin-gene-related peptide (CGRP) and chromogranin A was investigated in the developing rat (E18-adult) motor system, using immunofluorescence and confocal laser scanning, and compared with synaptic vesicle markers, synaptophysin and synapsin I. In lumbar motor perikarya CGRP-LI and Chr A-LI were present in high intensities in E18 and P1 perikarya in the anterior horn. With increasing age immunoreactivity decreased. Chr A-LI was sparse in the adult. In peroneal endplates, p38-LI and SYN I-LI were present in all stages, including E18. Peptide-LI was very weak or absent in early stages (E18 and P1), but abundant in P8 and P18, especially CGRP-LI, and decreased again in P32 and adult animals. These observations indicate that the peptides have precise functions during certain developmental stages, possibly related to synapse maturation, receptor concentration, and reduction of supernumerary endplates. Both peptides are rapidly transported anterogradely in adult motor axons, and may serve physiological functions also in the adult.
Muscle Nerve 1992 Sep
PMID:Development of calcitonin-gene-related peptide, chromogranin A, and synaptic vesicle markers in rat motor endplates, studied using immunofluorescence and confocal laser scanning. 151 19

A link between ABL oncogenes and MYC is suggested by the transformation synergy that is observed when MYC is expressed at high levels. Dominant negative MYC proteins were overexpressed in fibroblasts to determine if MYC complements ABL oncogene transformation or is essential for this process. Transformation by both v-abl and BCR-ABL oncogenes was reduced 5- to 10-fold, whereas transformation by the serine/threonine kinase oncogene v-mos was unaffected. Using a retrovirus construct modified to express BCR-ABL and MYC genes simultaneously, we show that dominant negative MYC suppressed transformation of primary mouse bone marrow pre-B cells by BCR-ABL. These observations demonstrate that c-MYC is essential for transformation and help define the pathway by which these proteins cause transformation.
Cell 1992 Sep 18
PMID:Dominant negative MYC blocks transformation by ABL oncogenes. 152 28

Activation of platelets with thrombin and other agonists causes a rapid increase in the phosphorylation of multiple proteins on tyrosine. To identify candidate protein-tyrosine kinases (PTKs; EC 2.7.1.112) that may be responsible for these phosphorylation events, we analyzed the expression of seven Src-family PTKs and examined the association of these kinases with known platelet membrane glycoproteins. Five Src-related PTKs were detected in platelets: pp60SRC, pp60FYN, pp62YES, pp61HCK, and two LYN products of Mr 54,000 and 58,000. The Fgr and Lck PTKs were not detected. Although strict comparative quantification of protein levels was not possible, pp60SRC was detected at higher levels than any of the other kinases. In addition, glycoprotein IV (GPIV, CD36), one of the major platelet membrane glycoproteins, was associated in a complex with the Fyn, Yes, and Lyn proteins in platelet lysates. Similar complexes were also found in two GPIV-expressing cell lines, C32 melanoma cells and HEL cells. Since PTKs appear to be involved in stimulus-response coupling at the plasma membrane, these results suggest that ligand interaction with GPIV may activate signaling pathways that are triggered by tyrosine phosphorylation.
Proc Natl Acad Sci U S A 1991 Sep 01
PMID:Membrane glycoprotein IV (CD36) is physically associated with the Fyn, Lyn, and Yes protein-tyrosine kinases in human platelets. 171 82


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