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)

We have studied the in vitro uptake of gallium-67 by exponentially growing EMT-6 sarcoma cells in long-term tissue culture. In this system, the addition of transferrin to the medium was required before an appreciable cellular uptake of Ga-67 occurred. The transferrin effect was complex, with an initial stimulation to a peak cell-to-medium ratio of 8--10:1 at low concentrations of transferrin (0.2 mg/ml), followed by a gradual decline in uptake as transferrin in the medium was increased further. EMT-6 tumor-cell uptake of Ga-67 was probably mediated by a specific cellular receptor for transferrin. Scatchard analysis of the EMT-6 cellular binding of human transferrin labeled with iodine-125 indicated a cellular receptor with affinity for transferrin of 5 X 10(6) l/mole and abundance of 500,000 receptors per cell. Over the experimental range of transferrin concentration in the medium, the observed uptake of Ga-67 was closely correlated with the degree of formation of Ga-67-labeled transferrin and the fraction of transferrin bound to the cellular receptor (N = 69, r = 0.86, p less than 0.0001).
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PMID:A transferrin-mediated uptake of gallium-67 by EMT-6 sarcoma. I. Studies in tissue culture. 54 30

The technique of laser resonance ionization mass spectrometry has been combined with isotope dilution analysis to determine iodine in oyster tissue. The long-lived radioisotope, 129I, was used to spike the samples. Samples were equilibrated with the 129I, wet ashed under controlled conditions, and iodine separated by coprecipitation with silver chloride. The analyte was dried as silver ammonium iodide upon a tantalum filament from which iodine was thermally desorbed in the resonance ionization mass spectrometry instrument. A single-color, two-photon resonant plus one-photon ionization scheme was used to form positive iodine ions. Long-lived iodine signals were achieved from 100 ng of iodine. The precision of 127I/129I measurement has been evaluated by replicate determinations of the spike, the spike calibration samples, and the oyster tissue samples and was 1.0%. Measurement precision among samples was 1.9% for the spike calibration and 1.4% for the oyster tissue. The concentration of iodine determined in SRM 1566a, Oyster Tissue, was 4.44 micrograms/g with an estimate of the overall uncertainty for the analysis of +/- 0.12 microgram/g.
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PMID:Determination of iodine in oyster tissue by isotope dilution laser resonance ionization mass spectrometry. 217 92

The diagnostic value of different laboratory methods in detecting Chlamydia trachomatis infections in high risk groups was analysed. The efficiency of a direct specimen test was compared with serology (IgG and IgM ELISA) and culture in L929 cells, stained either with fluorescein conjugated monoclonal antibodies or with iodine. Patients (no. = 1041) with localized genital infections attending a STD clinic, sexual contacts and patients with ascending infections from urological and gynecological clinics were examined. Chlamydia trachomatis was detected in 225 patients: 210 (93.3%) were reactive in the direct test (smears stained with monoclonal antibodies), whereas culture missed only 5 (sensitivity 97.8%) when stained by the same method. Cultures stained with iodine produced the lowest recovery rate (73.8%), but this rate increased to 80.9% when a second passage was performed. In addition the prevalence of Neisseria gonorrhoeae, Mycoplasma hominis, Ureaplasma urealyticum, Candida albicans and Trichomonas vaginalis was investigated. In patients with non-gonococcal urethritis (no. = 331) and cervicitis (no. = 353), Chlamydia trachomatis was isolated in 32.3% and 12.8% respectively. However, this pathogen could be isolated in only 3 (15.8%) out of 19 patients with epididymitis and 15 (14%) out of 107 patients with adnexitis, although 66.7% and 93.3% respectively had specific IgG antibodies. Specific IgM could by detected with a sandwich ELISA in patients with adnexitis (46.7%), epididymitis (33.3%), cervicitis (22.2%), non-gonococcal urethritis (14%) and in the sexual partners of patients with genital infections (35.7%). The direct specimen test with monoclonal antibodies is the method of choice for the diagnosis of a C. trachomatis infection in patients with urethritis and cervicitis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Diagnosis of Chlamydia trachomatis infection--culture versus serology. 245 16

Highly lipophilic and protein-bound derivatives of 1-(2-phenoxy-ethyl)-2-nitroimidazole (PENI; RGW-609), a known radiosensitizer, have been prepared by introducing one (IPENI) and two (DIPENI) iodine atoms into the phenyl ring via electrophilic substitution. The electron affinity of all 3 compounds, as determined by differential pulse polarography, was similar to that for MISO, a radiosensitizer which has undergone clinical trial, but P values were 2-3 orders of magnitude greater that for MISO and %PB values were as high as 30% in vitro compared to less than 1% for MISO. 131I-PENI was prepared by catalysed halogen exchange with Na131I in greater than 90% yield, and was found to be chemically and radiochemically stable in solution for at least 2 weeks. Whole-body studies in BDF/1 mice bearing EMT-6 tumors showed rapid hepatic extraction and biliary elimination with little or no accumulation in any other tissue including tumor and fat, indicating that P and % PB values had little impact on in vivo distribution and disposition. 131I-PENI was not measurably deiodinated in vivo. IPENI and DIPENI are radiosensitizers by inference only, that is, they have not been tested for radiosensitizer properties. However, PENI, the parent compound, has been shown to be active as a radiosensitizer, and the peak potentials (polarographic) for both IPENI and DIPENI fall near those of MISO, PENI and most other 2-nitroimidazole sensitizers. The low levels of concentration in target tissues achieved by 131I-PENI mitigate against its use as a diagnostic agent.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Electron-affinic compounds for labelling hypoxic cells: the synthesis and characterization of 1-[2-(2-iodophenoxy)-ethyl]-2-nitroimidazole. 654 17

Purified mouse submaxillary gland renin was labelled with iodine(125I) by the chloramine-T method and this 125I labelled renin was given to male ICR mice (6-7 wks. old), intravenously in a dose of 20 ng(2 microCi)/40 g body weight. At a specified time, the kidneys of these treated mice were excised, the radioactivity determined and the tissues immediately prepared for microscope and electron microscope autoradiography(micro-ARG and EM-ARG). Silver grains accumulated mainly at the apical site of the proximal convoluted tubules but were not identified in other areas of the nephron, including macula densa or in the arterial wall, glomeruli, and juxtaglomerular cells (micro-ARG). Silver grains were seen in the pinocytotic vesicles, vacuoles and lysosomal granules(EM-ARG). This is the first demonstration that exogenous renin is ultrafiltered through glomerular capillaries and is reabsorbed by pinocytosis in the one-third upper area of the proximal convoluted tubule.
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PMID:Distribution of exogenously administered renin in mouse kidney. 675 8

Three important factors are necessary for successful electron microscope autoradiography (EM-ARG): good resolution, proper preparation of the radioactive isotope (RI) labeled diffusible compounds, and shortened exposure time for ARG. The resolution problem is fundamental to EM-ARG. However, unless the diffusible RI compounds have been fixed correctly in the tissues during preparation, good resolution is useless. It is also necessary to shorten the exposure time for ARG. As yet, a high-speed ARG method fol electron microscopy has not been reported, although scintillation ARG methods have been applied to macro- and micro-ARG since 1960. High specific activity, a large amount of radioactivity per unit exposure for radio incorporation (incubation), and careful selection of labeled compounds that concentrate in the DNA or RNA of cell organelles may increase the sensitivity of the emulsion and shorten the exposure time for ARG. For example, labeled thymidine accumulates in nuclear DNA, 3H-SPG (Schizophyllan-produced polyglucan) is incorporated into lysosomal granules, and labeled iodine concentrates in thyroid follicles, often increasing the sensitivity of the emulsion and shortening the exposure time, but high-resolution ARG continues to be necessary, even though it requires 4 weeks or more of exposure time. Scintillation autoradiography using tritium seems unstable. We propose a new way to shorten exposure time for EM-ARG, by combining overdevelopment with coating both sides of the grid with emulsion. This method is approximately 100 times more sensitive than the conventional method, and only 4 days of exposure time are required, in contrast to the 1 month usually needed.
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PMID:High-speed electron microscope autoradiographic studies of diffusible compounds. 728 51

Apoptin, a small protein encoded by chicken anemia virus (CAV) was expressed in various human hematologic malignant cell lines derived from leukemias and lymphoma. Three of these cell lines contain bcl-2 or BCR-ABL proteins, known to block apoptosis induced by chemotherapeutic compounds. By immunofluorescence and propidium-iodide staining apoptin was shown to induce apoptosis in all analysed cell lines. Early after expression, apoptin exhibited a fine-granular distribution in the still intact nucleus. Later, apoptin became aggregated and the nucleus segmented. The data with truncated apoptin indicate that for optimal induction of apoptosis apoptin has to be located in the nucleus.
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PMID:Apoptin, a protein encoded by chicken anemia virus, induces cell death in various human hematologic malignant cells in vitro. 747 2

We have previously documented that glucocorticoids suppress the proliferation of BDS1 hepatoma cells, a rat epithelial tumor cell line derived from minimal deviation Reuber H35 hepatoma cells. Flow cytometry demonstrated that, after treatment with the synthetic glucocorticoid dexamethasone, the growth of an asynchronous population of BDS1 cells was arrested within one cell cycle which resulted in an accumulation of cells with a G1-G0-like DNA content. Consistent with a glucocorticoid-induced block early in the G1 phase of the cell cycle, propidium iodide flow cytometry revealed that addition of dexamethasone up to 2 h after release from contact inhibition prevented BDS1 hepatoma cells from entering S phase, whereas dexamethasone treatment after 2 h had no effect on the entry of cells into S phase. Moreover, dexamethasone treatment did not prevent BDS1 cells from entering S phase after release from synchronization at the G1-S boundary by a double thymidine block. Analysis of DNA content, [3H]-thymidine incorporation, and autoradiography of [3H]-thymidine-labeled nuclei revealed that, after release from dexamethasone, BDS1 cells synchronously reinitiated cell cycle progression and entered S phase 8 h after hormone withdrawal. Northern blot analysis demonstrated that the level of transcripts encoding the G1 marker genes CYL-1 and CYL-2 G1 cyclins peaked 4 h after dexamethasone withdrawal. Dexamethasone induced a 20-fold increase in the level of c-jun mRNA which was reversed after hormone withdrawal, whereas expression of c-fos transcripts remained at a low level during the time course of hormone treatment and withdrawal. Transient transfections with a collagenase-chloramphenicol acetyltransferase reporter gene showed that dexamethasone inhibited 12-O-tetradecanoylphorbol-13-acetate-inducible, but not basal, AP-1 transcription factor activity. Our results demonstrate that glucocorticoids reversibly induce an early G1 block in cell cycle progression of an epithelial tumor cell line that occurs with a coordinate elevation in the expression of c-jun transcripts.
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PMID:Glucocorticoids reversibly arrest rat hepatoma cell growth by inducing an early G1 block in cell cycle progression. 846 59

Inhibition of apoptosis (genetically programmed active cell death) by p210 BCR-ABL expression is a mechanism that might contribute to clonal expansion in chronic myeloid leukaemia (CML). Since cell death following exposure to ionizing radiation and many chemotherapeutic agents can occur by the apoptotic pathway, inhibition of apoptosis would be expected to confer a relative resistance to these treatments. Similarly, cells deprived of growth factors in vitro die by apoptosis, and inhibition of apoptosis would therefore be expected to allow cells to survive better in growth factor-deprived conditions. We found that the survival of normal and CML myeloid progenitors was the same after in vitro incubation in deprived conditions and after treatment with X-irradiation or glucocorticoids. We also found that mature cells in colonies produced by CML progenitors (CFU-GM) did not survive better than those produced by normal progenitor cells. Flow cytometric analysis of propidium iodide-stained cells provided a direct indication that the degree of apoptosis may correspond to the degree of deprivation. These results suggest that inhibition of apoptosis may not be the primary mechanism whereby BCR-ABL influences the expansion of the malignant clone in CML.
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PMID:Apoptosis in chronic myeloid leukaemia: normal responses by progenitor cells to growth factor deprivation, X-irradiation and glucocorticoids. 854 80

In 1996, the National Institute of Standards and Technology (NIST) released Standard Reference Material 1846 (Infant Formula), which can be used as a control material for assigning values to in-house control materials and for validating analytical methods for measurement of proximates, vitamins, and minerals in infant formula and similar matrixes. The SRM was manufactured by preparing a spray-dried formula base containing fat, protein, carbohydrates, and minerals and then combining that formula base with a dry-blend vitamin premix that supplied the vitamins. The Certificate of Analysis for SRM 1846 provides assigned values for concentrations of proximates (fat, protein, etc.), vitamins, and minerals for which product labeling is required by the Infant Formula Act of 1980 and by the Nutrition Labeling and Education Act of 1990. These assigned values were based on agreement of measurements by NIST and/or collaborating laboratories. Certified values are provided for vitamins A (trans), E, C, B2, and B6 and niacin. Noncertified values are provided for solids, ash, fat, nitrogen, protein, carbohydrate, calories, vitamin D, delta-tocopherol, gamma-tocopherol, vitamin B1, vitamin B12, folic acid, pantothenic acid, biotin, choline, inositol, calcium, phosphorus, magnesium, iron, zinc, copper, sodium, potassium, and chloride. Information values are provided for iodine, manganese, selenium, and vitamin K.
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PMID:Certification of nutrients in Standard Reference Material 1846: infant formula. 917 Jun 57


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