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The pituitary gland secretes in bursts: appraising the nature of glandular secretory impulses by simultaneous multiple-parameter deconvolution of plasma hormone concentrations.

To investigate patterns of endogenous hormone release, we have proposed a biophysical model in which measured hormone concentrations at any given instant reflect the operation of a suitable cumulation function (secretory input) convolved with an appropriate elimination mechanism (metabolic clearance). The cumulation function underlying a macroscopic hormone secretory burst can be represented by a random (Gaussian) distribution of instantaneous molecular secretory rates, which are centered with some finite and determinable standard deviation about a particular moment in time. The hormone elimination mechanism is described by a mono- or biexponential clearance function. The resultant convolution integral is solved by iterative nonlinear least-squares parameter estimation, in which all plasma hormone concentrations and their variances are considered simultaneously. Experiments with human endocrine time series revealed that the spontaneous secretory patterns of any of multiple distinct anterior pituitary hormones (luteinizing hormone, follicle-stimulating hormone, growth hormone, prolactin, thyrotropin, and adrenocorticotropic hormone) can be described effectively by this parsimonious model. In addition, endogenous hormone disappearance rates determined by deconvolution agreed well with those reported earlier that were determined after exogenous hormone injections. Moreover, this model predicted that durations of underlying secretory impulses are extremely brief; i.e., the standard deviations of the Gaussian distributions of instantaneous secretory rates range from 4.5 min (luteinizing hormone) to 16 min (growth hormone) compared to plasma hormone concentration peaks of 90-140 min in duration. Accordingly, we conclude that observed physiological patterns of fluctuating plasma hormone concentrations can be accounted for by distinct, highly delimited, random bursts of hormone release separated by intervals of secretory quiescence.

Adrenocorticotropic Hormone

Deconvolution of the fluorescence emission spectrum of human antithrombin and identification of the tryptophan residues that are responsive to heparin binding.

Heparin causes an allosterically transmitted conformational change in the reactive center loop of antithrombin and a 40% enhancement of tryptophan fluorescence. We have expressed four human antithrombins containing single Trp --> Phe mutations and determined that the fluorescence of antithrombin is a linear combination of the four tryptophans. The contributions to the spectrum of native antithrombin at 340 nm were 8% for Trp-49, 10% for Trp-189, 19% for Trp-225, and 63% for Trp-307. Trp-225 and Trp-307 accounted for the majority of the heparin-induced fluorescence enhancement, contributing 37 and 36%, respectively. Trp-49 and Trp-225 underwent spectral shifts of 15 nm to blue and 5 nm to red, respectively, in the antithrombin-heparin complex. The blue shift for Trp-49 is consistent with partial burial by contact with heparin, whereas the red shift for Trp-225 and large enhancement probably result from increased solvent access upon heparin-induced displacement of the contact residue Ser-380. The enhancement for Trp-307 may result from the heparin-induced movement of helix H seen in the crystal structure. The time-resolved fluorescence properties of individual tryptophans of wild-type antithrombin were also determined using the four variants and showed that Trp-225 and Trp-307 experienced the largest change in lifetime upon heparin binding, providing support for the steady-state fluorescence deconvolution.

Antithrombin III

A study of the application of a deconvolution method to scintigraphy.

It is shown that an Anger-type gamma camera can be considered as a linear filter. The image is therefore the convolution of the object by the camera point spread function. An important property of the objects is the fact that they are basically positive (count-rates as a function of space variables). The proposed deconvolution method (due to Biraud) is shown to work satisfactorily on a 1-D scintigraphic signal which is a particular cross-section of a 2-D image. This is a preliminary study of the enhancement of real scintigraphic images.

Image Enhancement

On the deconvolution of exponential response functions.

The deconvolution or unfolding of exponential response functions from experimental data has been examined through the use of a Bayesian based algorithm. The algorithm, which is founded upon the concepts of probability, ensures positivity of solution. This constraint leads to a significant reduction in the growth of statistical noise in deconvolved data when compared with the more common linear unfolding techniques. The algorithm is an iterative procedure which, in the absence of statistical noise, can ultimately result in complete signal recovery. When noise is present one must balance the degree with which the response function is removed against the growth in the noise and, at some point, terminate the iterative process. Criteria for determining the point at which this 'best estimate' is attained are examined and an operationally realisable test is given. Comparison of results is made with the inverse filter solution which, for an exponential response function, is shown to consist of the sum of the observed data and its first derivative.

Mathematics

On the possibility of obtaining non-diffused proximity functions from cloud-chamber data: I. Fourier deconvolution.

A mathematical procedure, using Fourier deconvolution, is described whereby diffusion-free proximity functions can be obtained from cloud-chamber data. Such non-diffused distributions can be used to obtain further microdosimetric and nanodosimetric quantities hitherto not available from experiments, thus making the cloud chamber an almost ideal nanodosimeter.

Fourier Analysis

Optimal filtering values in renogram deconvolution.

The evaluation of the isotopic renogram by means of the renal retention function (RRF) is a technique that supplies valuable information about renal function. It is not unusual to perform a smoothing of the data because of the sensitivity of the deconvolution algorithms with respect to noise. The purpose of this work is to confirm the existence of an optimal smoothing which minimises the error between the calculated RRF and the theoretical value for two filters (linear and non-linear). In order to test the effectiveness of these optimal smoothing values, some parameters of the calculated RRF were considered using this optimal smoothing. The comparison of these parameters with the theoretical ones revealed a better result in the case of the linear filter than in the non-linear case. The study was carried out simulating the input and output curves which would be obtained when using hippuran and DTPA as tracers.

Humans

Extravascular background subtraction using deconvolution analysis of the renogram.

The effect of the intravascular background in the renogram on the calculated renal retention function is known and can be removed. However, the effect of the extravascular background (EVB) has not been thoroughly investigated using patient data. By varying the size of the region of interest containing a single kidney and by deconvolving the 131I-hippuran and 99Tcm-DTPA renograms so generated, the following has been found: (a) the effect of EVB on the mean transit time (MTT) is negligible and EVB subtraction is not necessary, (b) the EVB overestimates the lower relative kidney function (RKF) and underestimates the higher RKF, so that EVB subtraction should be performed if the RKFs are asymmetric. A new method is described in which the correction for EVB is performed following deconvolution. If the RKFs are greater than about 30%, the correction can be performed using a regression equation between the RKFs corrected for EVB and those that are not corrected. When the RKFs are asymmetric to a greater extent, the correction should be performed for each study separately. The proposed method includes a small systematic error due to the inherent limitations of nuclear medicine equipment.

Adult

Perfect-mixer retention function by analytical deconvolution of tracer histograms: application to evaluation of left-ventricular contractility and competence.

The analytical solution for the perfect-mixer retention function, r(t), was developed from tracer histograms sampled at the system input, i(t), and its output, y(t), linked by the convolution integral y = i * r. Theories were developed for both continuous-output mixer and pulsatile, discrete mixer. The latter method was applied in first-pass radioangiography (FPRA) to calculate the forward ejection fraction of the left ventricle (LVFEF). Curves generated over the lungs and the ventricle provided system input and output respectively. LVFEF correlated strongly with the reference values obtained with simultaneously acquired gated FPRA(LVGEF) in 32 non-regurgitant patients: LVGEF = 0.90LVFEF + 5.93, r = 0.96, SEE = 3.98, p less than 0.001. In 14 patients with left-side valvular incompetence LVFEF values (0.41 +/- 0.13) were consistently lower than the corresponding LVGEF values (0.63 +/- 0.11). The method is free from instability inherent in numerical deconvolution. Applied in FPRA it yielded accurate estimates of LV contractility and competence. The continuous-mixer theory may apply to arbitrary compartmental models studied via tracer kinetics.

Adolescent

Characterization of attenuated proestrous luteinizing hormone surges in middle-aged rats by deconvolution analysis.

Reproductive aging in female rats is associated with attenuated preovulatory LH surges. In this study, detailed analyses of the episodic characteristics of the proestrous LH surge were conducted in young and middle-aged regularly cyclic rats. On proestrus, blood samples were withdrawn at 3-min intervals for 6 h and analyzed for LH concentrations by RIA in triplicate. Deconvolution analysis of immunoreactive LH concentrations revealed that there was no difference in the detectable LH secretory burst frequency between young and middle-aged rats. However, in middle-aged rats with an attenuated LH surge on proestrus, the mass of LH secreted per burst and the maximal rate of LH secretion per burst were only one fourth (p < 0.01) of those in young and middle-aged rats with normal LH surges. Furthermore, middle-aged rats with attenuated LH surges had a 4-fold decrease (p < 0.01) in the maximal rate of LH secretion per burst compared to young and middle-aged females with normal LH surges. The apparent half-life of endogenous LH was similar among the 3 groups. The attenuated LH surges of middle-aged rats were related specifically to a decrease in LH burst amplitude with no change in pulse frequency. The orderliness of moment-to-moment LH release as quantified by the regularity statistic, approximate entropy, was comparable in the 3 groups. Our findings of a markedly decreased amount of LH released per burst and preserved orderliness of the LH release process strongly suggest that a deficient GnRH drive and/or reduced responsivity to the GnRH signal, rather than altered timing of the signal, accounts for the age-related decline in reproductive function in female rats as presaged by an attenuated proestrous LH surge in middle age.

Aging

Scatter compensation in digital chest radiography using Fourier deconvolution.

The authors present a numerical deconvolution technique to compensate for image degrading effects caused by scattered photons in radiographic chest images. Fourier transform techniques are used to deconvolve a shift invariant model of the two dimensional point spread response functions of the scattered radiation. This approach uses a digitized radiograph acquired with a standard chest imaging protocol, so no specialized imaging equipment is required. While the shift variant shape of the scatter model is optimized for the lung field, effective compensation is provided when this model shape is applied to other chest regions. Preliminary evaluation suggests that this technique can provide improved image contrast over the entire chest region.

Computer Simulation

99Tcm-TDG renography with deconvolution analysis: a comparative study with 99Tcm-DTPA and 123I-hippuran.

TDG has been compared with hippuran and DTPA in normal subjects and the derived gamma camera renograms of both the whole kidney and parenchymal regions subjected to deconvolution analysis using the matrix algorithm. The transit time of TDG was found to be longer than both hippuran and DTPA. The parenchymal mean transit time of TDG was 3.0 +/- 0.6 min (mean +/- S.D.). That of hippuran was 2.2 +/- 0.7 min and DTPA, 2.6 +/- 0.5 min. It is thought that a small fraction of the TDG is bound to the renal parenchyma thus prolonging both the mean and maximum transit times.

Adult

The reduction of renogram deconvolution to a direct method of transit time determination.

It is known that the intrarenal mean transit time (MTT) can be determined using renography by first deconvoluing the kidney retention function from the obtained time-activity curve and then integrating the retention function. A direct and approximate calculational method, based on an integral mathematical model, has also been employed to estimate the MTT. In this work it is shown that the direct approximate method is equivalent to the standard deconvolution method applied with the assumption of a time independent retention function. Potential errors incurred using the direct method are thus quantified and assessed over a range of representative decay parameters.

Humans

99Tcm-MAG3 renogram deconvolution in normal subjects and in normal functioning kidney grafts.

This study provides values of transit times obtained by 99Tcm- mercaptoacetyl triglycine (99Tcm-MAG3) renogram deconvolution for both normal subjects and kidney graft recipients. The analysis included 50 healthy kidney units from 25 volunteers and 28 normal functioning kidney grafts. The parameters calculated for the whole kidney (WK) and for the renal parenchyma (P) were: mean transit time (MTT) and times at 20% (T20) and 80% (T80) of renal retention function initial height. For healthy kidneys the WK MTT was 174 +/- 27 s and P MTT 148 +/- 22 s. The WK T20 values were 230 +/- 33 s and P T20 231 +/- 34 s. The WK T80 was 108 +/- 19 s and P T80 106 +/- 12 s. Whole kidney and parenchymal values of transit times for normal functioning kidney grafts do not present significant differences with respect to healthy kidneys.

Adolescent

Renogram deconvolution in the management of diabetic nephropathy: utility of the measurement of initial tracer uptake.

Our objective was to assess mean transit time (MTT) and initial uptake, both parameters derived from the renal retention function (RRF), in the study of renal function in patients with diabetic nephropathy. We studied 25 patients, 7 with type I diabetes mellitus and 18 with type II diabetes mellitus, all of whom fulfilled the criteria for diabetic nephropathy with proteinuria and/or retinopathy. We found a statistically significant correlation between initial uptake and the other biochemical and renographic parameters studied except proteinuria: serum creatinine (r = 0.66, P < 0.002), creatinine clearance (r = 0.61, P < 0.003), glomerular filtration rate (r = 0.74, P < 0.003) and effective renal plasma flow (r = 0.66, P < 0.003). The other renographic parameters studied (maximal activity of the conventional renogram and MTT of the deconvoluted renogram) did not show any correlation. Initial uptake is a semi-quantitative renographic parameter that can provide complementary information to biochemical data and it may be useful in the management of diabetic nephropathy, especially in patients with high serum creatinine or creatinine clearance.

Adult

[Delimiting the molecular envelope of a protein by deconvolution of the Patterson function for native proteins].

A process, based on the superposition method, is described to delimit the molecular envelope of a protein by deconvolution of the Patterson function. The object is to obtain a preliminary set of phases from native structure-factor amplitudes with only native intensity data. The method has been tested with data from two immunoglobulin Fab fragments, Fab NEW and Fab R19.9. Several zones of resolution were explored.

Immunoglobulin Fragments

Deconvolution of tracer and dilution data using the Wiener filter.

In the study of living systems it is often necessary to inject or infuse a substance into the peripheral circulation and monitor its subsequent concentration in the plasma with time. Examples abound in the pharmacokinetic study of drugs and in the use of the indicator dilution technique for measuring blood flow. Furthermore, it is often necessary to deconvolve one such measured, and hence noisy, data set with another. One of the standard methods for deconvolving noisy signals is the Wiener filter, which is generally derived as a real window in the frequency domain such that the mean squared error between the estimated deconvolved function and the truth, on average, is minimized. Application of the Wiener filter requires some (often crude) model of the noise-to-signal power ratio as a function of frequency. In the pharmacokinetic and indicator dilution situations, however, one invariably has a good model of the actual function to be deconvolved in the form of a sum of decaying exponential functions. Such a model may be employed to calculate the signal-to-noise power ratio for use in the Wiener filter, or alternatively may be directly deconvolved itself. It is shown that better results are achieved with the Wiener filter if the model of the signal is not particularly accurate, whereas with a very accurate model it is better to deconvolve the model itself. The point at which the two deconvolution approaches perform comparably occurs when the error in the model is of a similar magnitude to the noise.

Mathematical Computing

Linear and nonlinear techniques for the deconvolution of hormone time-series.

Pulsatile hormone secretion is usually investigated by measuring hormone concentration in samples of peripheral plasma. In this paper, the deconvolution of hormone time-series to reconstruct the instantaneous secretion rate of glands is considered. Various techniques are discussed and compared in order to overcome the ill-conditioning of the problem and reduce the computational burden. In particular, linear techniques based on least squares, maximum a posteriori (MAP) estimation, and Wiener filtering are compared. A new nonlinear MAP estimator that keeps into account the non-Gaussian distribution of the unknown signal is worked out and shown to yield the best results. The performances of the algorithms are tested on simulated time-series as well as on series of Luteinizing Hormone (LH).

Algorithms

An automated film reader for DNA sequencing based on homomorphic deconvolution.

An automated reader for electrophoresis based DNA sequencing methods is described that provides fast and accurate sequence determination. Digitized sequencing lanes are processed with homomorphic blind deconvolution in preparation for peak detection, interlane alignment, peak refinement and base calling. Initial reads from direct blot sequencing films have error rates of about 1% at the rate of 5 nucleotides/s. Typical read lengths are 500-600 nucleotides. The described reader is a significant improvement over existing readers and could be an essential component in the sequencing efforts of the Human Genome Project.

Base Sequence