Biomedical subjects
Publications and source records attributed to T Uchikawa.
Explore the source record for details and available documents.
Stimulations or inhibitions by various agents of 45Ca efflux from prelabeled cells or tissues display distinct and reproducible profile patterns when the results are plotted against time as fractional efflux ratios (FER). FER is the fractional efflux of 45Ca from stimulated cells divided by the fractional efflux from a control unstimulated group. These profile patterns fall into three categories: peak patterns, exponential patterns, and mixed patterns. Each category can be positive (stimulation) or negative (inhibition). The interpretation of these profiles is difficult because 45Ca efflux depends on three variables: the rate of calcium transport out of the cell, the specific activity of the cell compartment from which the calcium originates, and the concentration of free calcium in this compartment. A computer model based on data obtained by kinetic analyses of 45Ca desaturation curves and consisting of two distinct intracellular pools was designed to follow the concentration of the traced substance (40Ca), the tracer (45Ca), and the specific activity of each compartment before, during, and after the stimulation or the inhibition of calcium fluxes at various pool boundaries. The computer model can reproduce all the FER profiles obtained experimentally and bring information which may be helpful to the interpretation of this type of data. Some predictions of the model were tested experimentally, and the results support the views that a peak pattern may reflect a sustained change in calcium transport across the plasma membrane, that an exponential pattern arises from calcium mobilization from an internal subcellular pool, and that a mixed pattern may be caused by a simultaneous change in calcium fluxes at both compartment boundaries.
Explore the source record for details and available documents.
The effects of cAMP, dibutyryl cAMP (DBcAMP), aminophylline, and imidazole on total cell calcium, calcium transport, and distribution were studied in cultured kidney cells by kinetic analysis of 45Ca uptake and desaturation curves. Low concentrations of the cyclic nucleotides (10(-7) and 10(-5) M) increase the total cell calcium, all intracellular exchangeable pools, and calcium transport between all cellular compartments. Aminophylline (1 mM) has effects qualitatively similar to cAMP and DBcAMP, while imidazole has opposite effects. At concentrations of 15 and 40 mM, imidazole depresses the total cell calcium and the cellular exchangeable calcium. Compared to the effects of parathyroid hormone (PTH), the changes obtained with 10(-7) and 10(-5) M cAMP are relatively modest, but higher concentrations (10(-3) M) of both cAMP and DBcAMP produce stimulations as marked as with 15 ng/ml PTH. The most dramatic changes are seen in the mitochondrial calcium pool and in the mitochondrial calcium exchange, which increase between 20- and 40-fold. These experiments show that cAMP mimics the effect of PTH on kidney cells and support the theory that cAMP is the mediator of PTH action on renal cell calcium transport.
Explore the source record for details and available documents.
This paper provides mathematical solutions for calculating calcium fluxes and compartments in isolated kidney cells from calcium-45 desaturation curves. In contrast to other available methods, these solutions allow the calculation of kinetic parameters even if isotopic equilibrium has not been reached at the beginning of the desaturation period. To test the validity of the method, calcium-45 desaturation experiments were performed in isolated kidney cells after labeling periods of 30, 60, 90, or 120 min. Even though the calcium-45 desaturation curves differ with different labeling times, the respective values of the calculated parameters are practically identical. The optical labeling period was found to lie between 60 and 120 min. Since this new method does not require initial isotopic steady state, it allows a formal kinetic analysis of tracer desaturation curves even after short periods of labeling.
This paper describes a method to measure calcium fluxes and calcium exchangeable pools in tissue slices by continuous perifusion in flow-through chambers. 45Ca desaturation from rat kidney slices can be analyzed as in an open three-compartment catenary system. A set of equations is given to calculate all the relevant kinetic parameters from the triple exponential equations which best fit the desaturation curves. The results show that the kinetic parameters obtained in kidney slices by this new method are in the same order of magnitude as those previously observed in cultured monkey kidney cells.
The effects of parathyroid hormone (PTH) on the transport and distribution of calcium in isolated kidney cells were studied by kinetic analysis of 45Ca desaturation curves. The results show that PTH (15 ng/ml) increases the total cell calcium content, every exchangeable pool, and all exchange rates. The greatest effect is observed in the slowest kinetic phase which reflects a mitochondrial pool. The effects of PTH occur even in the absence of magnesium and of phosphate and the larger effect is again obtained in the mitochondrial pool. These results suggest that PTH stimulates calcium transport in kidney cells by affecting the intracellular distribution of calcium or by stimulating calcium influx.
Ammonia has been known to be an inducing agent of hepatic coma associated with liver cirrhosis. In order to establish a non-invasive method of investigating the portal circulation and the metabolism of ammonia at liver the following studies were performed, by using cyclotron produced 13N-labeled ammonia and delayed line-camera interphased with on-line computer system. 1) Animal experiment. Dynamic scintigraphy of thoraco-abdominal region of a rabbit after intrasigmoidal as well as intravenous administration of 13N-ammonia were performed. 2) Theoretical consideration on the functional image of liver: According to the results of the animal experiments, a model of ammonia metabolism having the minimal complexity necessary to represent data in the case of intrasigmoidal administration was proposed. Starting from the solution to the differential equation describing the model, relevant parameters characterizing the dynamic curve of liver were duded.
1) Clinical application: Dynamic scintigraphy of liver and heart of a patient having liver cirrhosis after intrasigmoidal administration of 13N-ammonia (pH 8.1) were performed. Simultaneously, continuous measurments of radioactivity at the left side abdomen and the left temporal region were done by using a scintillation detector for renography. Successive measurement of radioactivity of blood was also carried out. 2) Comstruction of functional images of liver and heart: By using digital radioisotope image of liver and heart of the patient after intrasigmoidal administration of 13N-ammonia, the maps with respect to parameters described in the pervious paper were constructed.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.