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 microenvironmental factors on the regulation of intracellular pH (pHi) in MGH U1 cells and EMT-6 cells was studied using the fluorescent pH probe 2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein. Na+/H+ exchange and Na(+)-dependent Cl-/HCO3- exchange were found to be present in both cell types. The activity of both exchangers was dependent on pHi, with low levels of activity at neutral pH and an increase in activity as pHi fell. The level of extracellular pH (pHe) also influenced the operation of the exchangers, with a fall in activity as pHe was reduced over the range 7.4-6.6. This effect was more marked for the Na(+)-dependent Cl-/HCO3- exchanger than for the Na+/H+ antiporter, suggesting that under conditions of reduced pHe the Na+/H+ antiporter is the major mechanism for regulation of pHi. Neither 6 h of radiobiological hypoxia nor variations in the extracellular [Ca2+] over the range 1-6 mM had an effect on the regulation of pHi, while extracellular lactate (5-10 mM) caused a small, concentration-dependent decrease in the combined activity of both exchangers. We conclude that under the microenvironmental conditions found in some regions of tumors, Na+/H+ exchange may be the major method of regulation of pHi.
 ...
PMID:Regulation of intracellular pH in tumor cell lines: influence of microenvironmental conditions. 132 90

The removal of external Ca2+ ([Ca2+]o) reduces cytosolic Ca2+ ([Ca2+]i) in rat proximal tubules. In this report the role of external Na+ ([Na+]o) on the changes of [Ca2+]i and Ca2+ efflux caused by withdrawal of [Ca2+]o is described in rat renal proximal tubules. In aequorin-loaded tubules [Ca2+]i decreased from 235 +/- 25 to 48 +/- 16 (n = 4, P = 0.017), and 45Ca2+ fractional efflux ratio (45Ca2+ FER) increased from 0.94 +/- 0.03 to 1.64 +/- 0.19 (n = 6, P = 0.021) when Ca2+ was withdrawn from the bathing media of Krebs buffer (KB). The fall of [Ca2+]i, as well as the activation of 45Ca2+ FER, was reversed when [Na+]o in Ca(2+)-free KB was lowered isosmotically from 150 to 15 mM. However, when tubules were superfused with only 5 mM [Na+]o before [Ca2+]o was removed, [Ca2+]i also declined, but 45Ca2+ FER did not increase. The Na(+)-Ca2+ exchange inhibitor dichlorobenzamil (DCB) added after [Ca2+]o was removed evoked responses similar to [Na+]o removal, although DCB also inhibited internal Ca2+ release. These results are congruous with stimulation of Na+ influx in exchange for [Ca2+]i in Ca(2+)-free KB. However, even though total tubular Na+ was higher in Ca(2+)-free KB after 10 min, the initial rate of 22Na+ influx was not different without or with [Ca2+]o.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Na(+)-Ca2+ exchange and Ca2+ depletion in rat proximal tubules. 165 7

Pial arterioles of mice are studied by in vivo TV microscopy. Focal endothelial injury is produced by a laser/Evans blue technique. Moderate damage results in local platelet aggregation. Very slight damage, without electron microscopic evidence of injury, results in loss of many endothelium derived vasoactive factors. These include "EDRFs" for acetylcholine, bradykinin and calcium ionophore, and "EDCFs" for histamine and serotonin. In the cases of acetylcholine, histamine and serotonin, each agonist possesses an additional opposing action which is independent of endothelium. The latter action is unmasked by the endothelial injury. The balance between simultaneously acting endothelium dependent and endothelium independent actions is a determinant of the response to an agonist with two opposing actions. This balance is partly dependent upon initial tone. Thus the effect of the agonist depends on initial tone. One of the determinants of initial tone may be basal release of one or more EDRFs or EDCFs. Evidence in pial arterioles for the basal release of EDRF for acetylcholine, comes from our data showing that L-NMMA constricts these arterioles. L-NMMA is a known inhibitor of synthesis of "classical" EDRF from L-arginine. The response to L-ARG is relaxation. Both the response to L-NMMA and the response to L-ARG are abolished by laser/dye injury of the endothelium. Thus these agents are really acting via an endothelial mechanism in brain arterioles, just as has been reported for their actions in conductance vessels. Finally mild injury associated with loss of "EDRFs" is also accompanied by a reduced ability of pial arteriolar endothelium to repell activated platelets.
 ...
PMID:Control of brain microcirculation by endothelium. 225 25

In recent years, laboratory testing in the critical-care setting has increased, a trend due, in part, to the evolution of electrochemical sensors. Various innovations have extended sensor lifetimes, reduced sensor maintenance, and led to the development of single-use and unit-use disposable sensors. These sensor technologies allow the accurate and precise determination, either at or near the bedside, of several analytes including pO2, pCO2, pH, Na, K, Cl, ionized calcium, hematocrit, total hemoglobin, and glucose. Use of these new systems, however, has raised new issues regarding sensor calibration and sample handling and collection. The number of direct-reading analyzers for electrolyte determinations has also increased dramatically. Issues regarding calibration of ion-selective electrodes (ISEs) for Na/K have also been raised after demonstrations of between-instrument variation. Recently, collaborative efforts between eight ISE instrument manufacturers and the National Institute of Standards and Technology resulted in the development of a Standard Reference Material, SRM 956, for the purpose of standardizing direct-reading Na/K ISEs to the flame photometer. Other widely used technologies that provide noninvasive, continuous monitoring include pulse oximetry and transcutaneous gas electrodes. These trends are expected to continue and to produce a new generation of electrochemical and optical sensors.
 ...
PMID:Current analytical approaches to measuring blood analytes. 238 68

Factors affecting the esterification rate of cholesterol by lecithin cholesterol acyltransferase (LCAT E.C. 2.3.1.43) in native cold labelled substrates (human, rabbit, rat serum, plasma, VLDL, LDL depleted serum, rabbit intraocular fluids) repaired by use of ready-made 14C-cholesterol discs (Cholesterol kinetics LCAT-test, UVVVR, Czechoslovakia) were investigated. EDTA added to the serum during the cold incubation (18 h, 0 degrees C-4 degrees C) increased the rate of esterification due to elimination of Ca2+ ions. The similar stimulating effect was found in the presence of mercaptoethanol (ME) in the serum, while in the plasma already stimulated by EDTA no additional effect by ME could be noticed. Freezing and thawing did not affect the fractional esterification rate (FER-per cent of total serum unesterified cholesterol esterified per hour) in normolipidaemic sera, whereas in hyperlipidaemic sera, particularly those with high levels of VLDL, FER was stimulated. Esterification partially proceeded during the cold incubation of serum or plasma with 14C-cholesterol ready-to-use discs, attaining the values of about 0.3%/h and 2-6%/h, respectively, in human sera and in rabbit and rat sera. The starting level of esterification did not affect the linearity of LCAT reaction during warm incubation (30 min at 37 degrees C), neither was the absolute value of FER changed as compared with cold labelled sera with those inhibited by DTNB and reactivated by ME. Substantial LCAT activity was also detected in extremely diluted substrates--such as intraocular fluid collected from rabbits with induced uveitis or after preceding paracentesis.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Factors influencing the cholesterol esterification rate in lecithin cholesterol acyltransferase radioassay. 294 8

The measurement of total calcium (CaT) in biological fluids by flame atomic absorption spectroscopy (FAAS) is one of the more accurate yet practical methods available today. With attention to details at every analytical step, the imprecision of FAAS outlined above can be as low as +/- 0.01 mmol/liter at the 2.65 mmol/liter upper reference level of CaT found in the serum of healthy young adults (a CV of 0.4%). The accuracy of FAAS as judged by measurements of NBS/SRM #909, a lyophilized serum material carrying CaT values assigned by isotope dilution mass spectrometry, can be within +/- 1% (recovery of 99-101%) or less in skilled hands. As our brief section on application suggests, FAAS methods for CaT can be adopted to provide rapid and accurate results in many different biological fluids and tissues.
 ...
PMID:Measurement of total calcium in biological fluids: flame atomic absorption spectrometry. 337 81

The hemodynamic effects induced by thiopental and a decrease in blood ionized calcium are uniform. This investigation was undertaken to show a possible decrease in ionized blood calcium during induction of general anesthesia with thiopental. Twenty-four patients aged 19-79 years (median 57) were studied. None had any known parathyroid disease, malabsorption, or chronic renal insufficiency, and none were receiving calcium channel blockers. For the analysis of blood Ca++, pH, and PCO2, blood samples were drawn anaerobically into a heparinized syringe from an i.v. cannula. A special heparin solution was used (S4500 Radiometer, Copenhagen) to avoid the influence of heparin on the Ca++ determination. The initial 2 ml were discarded. No samples were drawn in the first 3 min after removal of the tourniquet. A maximum of 100 ml isotonic saline was infused between the two samplings. The infusion was stopped for at least 30 s before sampling. PCO2, B-Ca++, and pH were measured directly using the ABL 4 (Radiometer, Copenhagen) and the ICA 1 ionized calcium analyzer (Radiometer, Copenhagen). The standard deviation of repeated measurements of B-Ca++ within a short time using the same sample is 0.01 mmol/l on the ICA 1. The samples were drawn just before and 2 min after thiopental injection (median 5.9 mg/kg) was started. The pulse and blood pressure were simultaneously measured. The individual Ca++ measurements are shown in Table 1. The results of the investigation are shown in Table 2.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Effect of thiopental Na on the concentration of calcium ions in blood]. 366 52

The role of calcium in initiating smooth muscle contraction is widely accepted. The sources of this calcium are thought to be located both intracellularly and extracellularly. We have recently developed a method by which the cellular localization of calcium in smooth muscle can be determined. This method involves exposing the tissue to 45Ca, rapidly freezing and vacuum dehydrating the tissue, and preparing the tissue for electron microscopic autoradiography (EM ARG). In the present study the distribution of calcium in control and potassium-contracted tissue of the rabbit vas deferens was compared. No significant differences in distribution were observed in the two treatments. This finding provides morphological support for the hypothesis that the calcium used in potassium-induced contraction is primarily of extracellular origin. In addition, significant sequestration by intracellular organelles does not occur during a potassium contraction. In other experiments, the effect of rinsing tissue in cold calcium prior to freezing was investigated. From these data is appears that calcium is removed from the cytoplasmic matrix, plasma membrane, and organelles in a nonuniform manner. Further investigation into these findings should enable us to characterize more precisely the intracellular redistribution of calcium that occurs as a result of a variety of physiological manipulations.
 ...
PMID:The cellular distribution of calcium in freeze-dried rabbit vas deferens using EM autoradiography. 397 81

In Figure 13 we have tried to summarize the interactions of thermal and nonthermal control of effector responses, the effects these responses have on the body during exercise, and the ways the changing state of the body feeds back on the central control systems. These systems were depicted in Figure 3 and are included in condensed form in Figure 13. Exercise affects thermoregulatory responses not only by increasing heat production, but also through a number of other mechanisms. For example, the thermoregulatory responses tend to reduce central venous pressure, and sweating without fluid replacement will increase plasma osmolality. The secondary effects of these changes on the control of the thermoregulatory responses may themselves have an important effect on the rise in Tc during prolonged exercise or exercise in the heat. In concluding, it is appropriate to briefly answer the questions raised in the introduction. In our view, the concept of shifting the set point is not different from the concept of resetting the "thermostat," and the temperature regulatory system is governed by only one set point, which does not change during exercise. Tsk does not change the set point as we have defined it. Rather it combines with thermal information from the core and other deep body thermo-detectors to produce a thermoregulatory command signal Tws distributed to all effector responses. To demonstrate a set point shift, one must show that the Tws thresholds for initiating all heat-dissipating responses shift in the same direction. Although this does not occur with exercise, it does occur with time of day, heat acclimation, endurance training, and fever. A hyperosmolar state also can raise the threshold for sweating and vasodilation uniformly, and therefore may also raise the set point. However, a change in posture, for example, which alters the threshold for vasodilation but not for sweating, does not alter the set point. We believe that a shift in threshold for a given effector may be produced by either a central or a peripheral mechanism. For example, an ion-osmotic influence on the sweating: Tc threshold may be at the level of the central nervous system or the sweat gland itself. However, a set point shift must be a central event, since it influences all effector responses uniformly. Is the set point governed by the ratio of sodium to calcium ions in the posterior hypothalamus? This is unlikely. Shifts in ion concentration can influence effector responses, but they do not appear to shift all effectors uniformly.
 ...
PMID:Temperature regulation during exercise: old concepts, new ideas. 637 37

Reference systems in clinical chemistry, whether loosely structured or highly organized like the National Reference System for Clinical Chemistry (NRSCC) in the USA are built upon an assemblage of interrelated materials, methods, and agreements. For example, the NRSCC Council has accepted the following items for the measurement of total calcium in human serum: 1) the Reporting Unit (the SI non-coherent molar concentration unit-mmol/l), 2) a Certified Reference Material (NBS/SRM 915 CaCO3), 3) a Definitive Method (IDMS) and 4) a Reference Method (FAAS). Recently, the IDMS measured calcium value has become available on a freeze-dried human serum (NBS/SRM 909) and allows the direct accessment of the accuracy of routine methods, instrument systems, calibrators and control materials. Utilizing the NRSCC reference method and materials for total calcium measurements and the Radiometer System (ICA1) for ionized Ca2+ measurements, we have begun to ask the question, "What are the essential items in a reference system for ionized calcium?" As expected, our initial explorations reveal more problems than answers, thus our very limited and unsophisticated initial data will be presented primarily as a means to ensure discussion. Despite, the electrochemical complexity of the electrochemical interactions, and the technologic differences from one measuring system to another, it is my belief that a reference system capable of widespread acceptance for ionized Ca2+ must be introduced to ensure the long-term integrity and interlaboratory compatibility of this vital physiological measurement.
 ...
PMID:A reference system for ionized calcium. 657 76


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