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 describe the application of macroautoradiography, a relatively simple, quantifiable method for the evaluation of positron-emitting and gamma-emitting radiopharmaceuticals. We have investigated the response properties of two types of film to positron (F-18) and negatron (C-14) emitters. Variations in the response of film to increasing film-to-source distance are described, along with the effects of different intensifying screens and mounting tape. Digitization of whole-body autoradiograms (WBARG) in small animals was performed by using a videodensitometry system (videocamera interfaced to a computer). Quantitation was derived from analysis of a series of step-wedge standards that covered the range of radioactivities in the sample. By using a close-up lens on the videocamera, a 2- by 2-cm field is digitized as a 128 X 128 array, each pixel representing 156 X 156 micron. The effect of chlorpromazine (CPZ) on glucose metabolism in mice was studied by giving C-14 2DG followed by CPZ and F-18 FDG in the same animal. Muscle activity decreased and brown-fat activity increased. The high spatial resolution of this technique enables quantification in structures as small as the basal ganglia in mice. The use of dual-nuclide ARG permits each animal to be its own control, which greatly increases the utility of this method.
...
PMID:Quantitative autoradiography with radiopharmaceuticals, Part 2: Applications in radiopharmaceutical research: concise communication. 640 73

An epithelial cell line, designated CHK-ACE, was established from the kidney of a spontaneously diabetic Chinese hamster from the highly inbred AC line. CHK-ACE was separated into two sublines, CHK-ACE-100 and CHK-ACE-400, by successive passages in 100 and 400 mg/dl glucose respectively. Extra- and intracellular activities of N-acetyl-beta-D-glucosaminidase and beta-D-galactosidase were measured in these cultures after exposure to varying concentrations of glucose (100, 200, 300 and 400 mg/dl) for one passage and 10% heated fetal calf serum for 6.5 h before enzyme measurements were taken; no apparent dependence on medium-glucose concentration was found. In serum-free medium, the time-dependent release of both N-acetyl-beta-D-glucosaminidase and beta-D-galactosidase was sustained for up to 24 h; no significant difference in their activities was found between CHK-ACE-100 cultures grown in 100 and 400 mg/dl glucose for one passage.
...
PMID:Acid glycohydrolase in Chinese hamster with spontaneous diabetes. VII. The lack of short-term glucose-effect in cultured kidney cells. 678 22

An epithelial cell line established from a Chinese hamster kidney, CHK-ACE, was separated into two sublines, CHK-ACE-100 and CHK-ACE-400, by 18 successive passages in medium containing 100 and 400 mg/dl glucose, respectively. Binding of CHK-ACE-100 and CHK-ACE-400 cell to 125I-labeled insulin showed similar pH and time dependency; 125I-labeled insulin, concentration differed in the two sublines, however. Degradation of 125I-labeled insulin, as determined by its ability to bind insulin antibody and cells, was more extensive when preincubated with CHK-ACE-400 cell than with CHK-ACE-100 cells. When CHK-ACE-100 cells were grown in 400 mg/dl glucose for six passages, these cells showed more insulin binding sites than cells grown parallel in 100 mg/dl glucose; whereas CHK-ACE-400 cells grown in 100 mg/dl glucose for six passages showed fewer insulin binding sites than those grown parallel in 400 mg/dl glucose. A slight increase in Kf/Ke ratio was observed in both sublines when grown in 400 mg/dl glucose as compared to 100 mg/dl glucose, indicating attenuated negative cooperativity of the binding sites in cells grown in 400 mg/dl glucose. Tunicamycin, at concentrations from 0.016 to 0.125 micrograms/ml, showed no direct effect on the assay of 125I-labeled insulin binding to CHK-ACE-100 cells; exposure of CHK-ACE-100 cells to tunicamycin, at concentrations from 0.01 to 0.2 micrograms/ml, for 24 h caused a dose-dependent decrease in insulin binding capacity and an increase in Kf/Ke ratio. These data indicate that the number of insulin binding sites in the cultured Chinese hamster kidney epithelial cells increased with high glucose concentrations in the culture medium, whereas tunicamycin, an inhibitor of protein glycosylation, lowered the number of insulin binding sites.
...
PMID:Insulin binding in cultured Chinese hamster kidney epithelial cells. The effects of glucose concentration in the medium and tunicamycin. 702 31

Intravenous glucose tolerance tests (IVGTT) with simultaneous assessment of plasma insulin and analyses of the fatty acid composition of serum lecithin and cholesterol esters were performed in 11 women with previous gestational diabetes before and repeatedly during 6 months' administration of a low-dose progesterone (lynestrenol = LYN). 8 of these women were also followed in an identical manner during 6 months of nonhormonal contraception (intrauterine device = IUD) and additionally 6 of these women were followed also during the use of a combined oral contraceptive (OC) (ethinyl estradiol + lynestrenol - EE + LYN). LYN did not alter the IVGTT or plasma insulin but decreased the proportion of polyunsaturated fatty acids (PUFA) in serum lecithin (p less than 0.01) and cholesterol esters (p less than 0.01) where oleic acid was reciprocally increased (p less than 0.05). After 6 months' use of IUD, on the other hand, the k value of IVGTT increased by 45% (p less than 0.01) without significant changes in plasma insulin. In both lecithin and cholesterol ester PUFA increased (p less than 0.05) and cholesterol ester oleate decreased (p less than 0.01); i.e., virtually the reversal of the changes seen during LYN administration. The combined OC, EE + LYN, caused a decrease in the k value by 27% (p less than 0.05) which was apparent even when compared to the effects of LYN alone. EE + LYN also increased (p less than 0.05) lecithin palmitate and decreased stearate (p less than 0.05) and had a concomitant tendency to lower PUFA and increase oleic acid in both lecithin and cholesterol esters. These results indicate that LYN has little influence on the glucose tolerance in women predisposed to diabetes but may provide poorer conditions for dietary treatment of subclinical diabetes than do nonhormonal IUDs. The combined CO, EE + LYN, on the other hand, promptly diminishes glucose tolerance and may also have an unfavorable influence on liver metabolism.
...
PMID:Metabolic studies in gestational diabetic women during contraceptive treatment: effects on glucose tolerance and fatty acid composition of serum lipids. 703 4

Twenty-three young women with insulin-dependent diabetes were randomly allocated to contraceptive treatment with either a progestogen only (Lynestrenol 0.5 mg) (LYN) or a combined oral contraceptive (OC) (ethinyl estradiol 50 micrograms + lynestrenol 2.5 micrograms) (EE + LYN). After six months treatment the medication was withdrawn for at least two months, after which the patients were placed on the other preparation. Diabetes control and serum and high density lipoprotein (HDL) lipids were assessed before and after 1, 3 and 6 months of treatment. Low-dose LYN administration did not alter the insulin requirement, blood glucose or body weight while the combined EE + LYN treatment increased the insulin requirement (p less than 0.01) without altering blood glucose or body weight. Low-dose LYN reduced serum triglycerides (p less than 0.001), serum cholesterol (p less than 0.001) and serum phospholipids (p less than 0.01) without affecting HDL lipids, while EE + LYN gave an inconsistent increase in serum triglycerides (p less than 0.01) but no change in HDL lipids. These findings confirm our earlier results and we conclude that EE + LYN influences diabetes control slightly more (although still not seriously) than the low-dose LYN. It is suggested that insulin-dependent diabetics (in contrast to non-diabetics) are more sensitive to the influence of 19-norprogestogens than to alkylated estrogens, with respect to lipid metabolism.
...
PMID:Oral contraception in diabetic women. A cross-over study on serum and high density lipoprotein (HDL) lipids and diabetes control during progestogen and combined estrogen/progestogen contraception. 704 Jan 92

The effects of altering skin and core temperature by cold exposure and exercise on substrate mobilization and utilization were examined. Six subjects between the ages of 22-27 years rested and exercised in neutral and cold environments to produce 1) a neutral core and neutral skin temperature, 2) a neutral core and cold skin temperature, and 3) a cold core and cold skin temperature. Free fatty acid (FFA), glucose (GL), Lactate (LA), hemoglobin (Hb), and hematocrit (Hct) concentrations were measured along with heart rate (HR), respiratory exchange ratio (R) and oxygen consumption (VO2) after 30, 60, and 90 min of exposure to each condition. FFA, GL, LA, Hb, and Hct concentrations increased significantly during rest when both mean skin temperature (Tsk) and rectal temperature (Tre) were reduced. Plasma FFA concentration was also significantly elevated and R values were reduced during exercise when both Tsk and Tre were lowered compared to exercise in a neutral environment. No significant differences in substrate concentration, hemoconcentration, or R values were observed when Tsk alone was reduced at rest or during exercise. It is concluded that a preferential utilization of fat occurs during exercise in the cold when both Tsk and Tre are reduced compared to exercise in a neutral environment.
...
PMID:The effects of rest and exercise in the cold on substrate mobilization and utilization. 715 40

Dietary composition has been strongly implicated as an important determinant of in vivo insulin sensitivity. However, the metabolic alterations associated with extreme changes in diet have not been well described. We compared glucose metabolism after a standard diet ([STD] 35% fat, 51% carbohydrate, and 14% protein) with the effects of a 3-week adaptation to a low-carbohydrate, high-fat diet ([LCD] 75% fat, 8% carbohydrate, and 17% protein). Ten healthy men were studied using the euglycemic clamp technique, indirect calorimetry, and percutaneous vastus lateralis muscle biopsies for analysis of glycogen synthase (GS) and pyruvate dehydrogenase (PDH) activities in the basal and insulin-stimulated states. Insulin-stimulated glucose disposal was unchanged (STD 46.1 +/- 4.3 v LCD 46.0 +/- 4.3 mumol/kg.min, P = NS), but marked alterations in the routes of glucose disposal were noted. Insulin-stimulated glucose oxidation (Gox) was markedly reduced following LCD (STD 18.6 +/- 1.9 v LCD 8.23 +/- 1.9 mumol/kg.min, P = .0001), and nonoxidative glucose metabolism (Gnox) was enhanced by LCD (STD 24.9 +/- 0.9 v LCD 38.9 +/- 4.3 mumol/kg.min, P = .03). Following LCD, both the total and active forms of PDH (PDHt and PDHa) were significantly depressed. After LCD, GS activates (FV0.1, %I, and A0.5) were unaffected in the basal state, but were greater than for STD (P = .004) after insulin stimulation. The apparent increase in the sensitivity of GS to activation by insulin following LCD correlated strongly with maximal O2 consumption ([VO2max] r = .97, P = .001), suggesting that physical conditioning interacted with the metabolic impact of LCD. In summary, LCD did not induce changes in net glucose disposal.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Low-carbohydrate diet alters intracellular glucose metabolism but not overall glucose disposal in exercise-trained subjects. 747 82

An increased spontaneous and stimulated growth hormone (GH) secretion is well documented in insulin-dependent diabetes mellitus. On the contrary, in non-insulin-dependent diabetes mellitus (NIDDM) conflicting results arise from literature. In 14 patients with NIDDM, 7 normal weight (NWD) and 7 obese (OD), we investigated the somatotrope responsiveness to GHRH (1 microgram/kg) alone or combined with arginine (ARG, 0.5 g/kg), which is able to enhance the GH response to GHRH, probably by inhibiting somatostatin release from hypothalamus. Baseline IGF-I, IRI FFA and glucose levels were also determined. Twelve healthy normal subjects (NS) and 12 obese patients (OP) were evaluated as control groups. GH but not IGF-I levels were higher (p < 0.05) in NS than in OP (1.5 +/- 0.5 vs 0.5 +/- 0.2 microgram/l). Insulin levels were higher (p < 0.05) in OP than in NS, NWD and OD (18.7 +/- 1.8 vs 8.7 +/- 0.5, 6.4 +/- 1.9 and 11.8 +/- 1.2 microU/l). FFA were higher (p < 0.05) in NWD. OD and OP than in NS (0.69 +/- 0.04, 0.70 +/- 0.04 and 0.65 +/- 0.06 vs 0.39 +/- 0.03 mmol/l). Plasma glucose was higher (p < 0.05) in diabetic patients than in normal and obese subjects. GH responses to GHRH in NWD, OD and OP were similar (AUC: 221.6 +/- 33.3, 206.0 +/- 35.9 and 177.2 +/- 57.3 micrograms/l/min, respectively) and all lower (p < 0.05) than that in NS (776.7 +/- 206.5 micrograms/l/min). ARG determined a significant increase of GHRH-induced GH release in all groups (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Blunted GH response to growth hormone-releasing hormone (GHRH) alone or combined with arginine in non-insulin-dependent diabetes mellitus. 772 89

A microbiological assay to detect different chemical compounds of selenium for potential future use in the study of the distribution of these chemical forms in foods is being developed. This assay is based on the detection, by infrared analysis, of CO2 in a culture of Escherichia coli when the bacteria are grown in the presence of various selenium compounds. The CO2 production is the result of selenium-dependent formate dehydrogenase activity, which catalyzes oxidation of formic acid produced during glucose metabolism. Smooth response curves were generated over several orders of magnitude for selenocystine, selenite, and selenomethionine. The assay detects selenium concentrations (above background) as low as 1.5 nM for selenocystine and selenite and 4 nM for selenomethionine in minimal medium. Detection of selenomethionine was enhanced (to a sensitivity of 1.5 nM) by the addition of methionine to minimal medium and was enhanced even further (to a sensitivity of 0.8 nM) by the addition of a defined mixture of amino acids. Selenomethionine could be assayed in the presence of an amino acid concentration which is proportional to the amino acid/elemental selenium ratio found in a wheat gluten reference material (NIST SRM 8418). This implies that the assay can detect selenium compounds in a variety of foods at low concentrations, avoiding the background CO2 production caused by high concentrations of non-selenium-containing amino acids. The observation that methionine enhanced selenomethionine availability for formate dehydrogenase synthesis supports studies in animals demonstrating that methionine controls selenomethionine incorporation into selenoenzymes.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Optimization of an Escherichia coli formate dehydrogenase assay for selenium compounds. 781 Oct 71

The extracellular pH (pHe) in solid tumors is frequently lower than the pHe in normal tissues, but the intracellular pH (pHi) is regulated to physiological levels. Cell killing can be achieved in an acidic environment in tissue culture by nigericin, which acidifies cells by transporting H+ from the extracellular space into the cytoplasm; this cell killing can be enhanced when used with 5-(N-ethyl-N-isopropyl)amiloride (EIPA), a potent inhibitor of membrane-based Na+/H+ exchange, which plays a major role in the regulation of pHi (R. P. Maidorn; E. J. Cragoe; I. F. Tannock, Br. J. Cancer 67:297-303; 1993). We have therefore assessed the ability of nigericin and EIPA to kill cells in two murine solid tumors (the KHT fibrosarcoma and the EMT-6 sarcoma). Hydralazine, which reduces tumor blood flow, or glucose, which stimulates glycolysis leading to accumulation of lactate, were also administered to mice to lower pHe in the tumors. We observed only a small decrease in the surviving fractions of cells in the tumors when tolerated doses of nigericin and EIPA were given IP to tumor-bearing mice. When nigericin and EIPA were combined with administration of hydralazine, the surviving fraction of cells in both tumors was reduced by a factor of 0.01, but there were minimal effects on growth delay. Administration of glucose with nigericin and EIPA led to a smaller reduction in surviving fraction of the KHT tumor (by approximately 0.1), although glucose was more effective than hydralazine in lowering the mean tumor pHe. When KHT tumors were treated with 15 Gy X-rays followed immediately by nigericin, EIPA, and hydralazine, a reduced surviving fraction as well as an increase in tumor growth delay was observed compared to radiation alone; however, there was little evidence to suggest that these agents were selectively toxic to the cells that survived radiation. Nigericin and EIPA, with or without hydralazine, had minimal effects on normal tissues, as assessed by changes in body weight, number of leukocytes, and serum creatinine levels. We conclude that pharmacological effects to acidify cells and to prevent regulation of pHi under the acidic conditions that exist in solid tumors can lead to moderate levels of cell killing, if additional strategies are used to lower tumor pHe.
...
PMID:Antitumor activity of nigericin and 5-(N-ethyl-N-isopropyl)amiloride: an approach to therapy based on cellular acidification and the inhibition of regulation of intracellular pH. 786 1


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---