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Biomedical subjects

E de Boer

Publications and source records attributed to E de Boer.

At least 109 records · Page 6Linked to original sources
PubMed1981

Structure and expression of a cloned beta o thalassaemic globin gene.

We have cloned the single beta-globin gene from an Italian patient who is a double heterozygote for beta o/delta beta o thalassaemia. RNA isolated from nucleated red cells from this patient can be translated in vitro to give detectable levels of A gamma- G gamma and alpha-globin, but no beta-globin. S1-mapping transcription studies show that beta-globin mRNA is present at about 1-3% of the level of alpha- and gamma-globin mRNA. In addition, the expression of this gene has been studied by reversed genetics. SV40-plasmid-beta o-globin gene recombinants have been transfected into Hela cells and analysed for beta-globin mRNA. In contrast to the results obtained with mRNA isolated directly from the blood of this patient, in the transfected Hela cells the same level of beta-globin mRNA is seen for the beta o thalassaemic globin gene and for a normal beta-globin gene. To elucidate the nature of the lesion, the entire DNA sequence of the beta-globin gene of this patient has been determined. The sequence shows that this gene contains a termination codon at position 39 (CAG - greater than UAG). Otherwise, there is a remarkable conservation of the entire DNA sequence.

Base Sequence↗
PubMed1981

Isolation of beta-globin-related genes from a human cosmid library.

A human gene library was constructed using an improved cloning technique for cosmid vectors. Human placental DNA was partially digested with restriction endonuclease MboI; size-fractionated and ligated to BamHI-cut and phosphatase-treated cosmid vector pJB8. After packaging in lambda phage particles, the recombinant DNA was transduced into Escherichia coli 1400 or HB101 followed by selection on ampicillin for recombinant E. coli. 150 000 recombinant-DNA-containing colonies were screened for the presence of the human beta-globin related genes. Five recombinants were isolated containing the human beta-globin locus and encompassing approx. 70 kb of human DNA.

Bacteriophage lambda↗
PubMed1981

Digital solution of cochlear mechanics problems.

Several advantages are incurred when the greater part of the solution to a cochlear mechanics problem is carried out with an analytical method. Many cochlear mechanics problems can be formulated in such a way that they require solution of a specific integral equation in terms of the Fourier transform W(k) of the BM velocity w(x). An analytical solution for W(k) is possible for a certain class of impedance functions. In this paper it is shown how the Fourier transformation to the x domain can be carried out without producing aliasing errors. The impedance function Z(x) must be made periodic in x. For a particular choice of this function, one which puts the main emphasis on BM resonance, the solution to the integral equation can be found from a simple recurrence relation between the spectral components Wn of w(x). The method is illustrated for typical one-, two-, and three-dimensional cochlea models. It is proven that in the region of resonance for (nondigital) solution method published earlier produces nearly equivalent results. The digital method has a much wider scope of application.

Biomechanical Phenomena↗
PubMed1980

Deep-water waves in the cochlea.

In order to obtain physical insight from a mathematical solution of the cochlear mechanics problem, a delicate balance is required between simplifications and refinements in modeling. For the study of the transition of long to short waves (deep-water waves) a closed-form solution is advantageous; this can, however, only be obtained at the cost of further simplification. In previous work the course of the impedance function z(x) was, therefore, reduced to the extreme: in the neighbourhood of the resonance location z(x) was assumed to be a linear function of x - the so-called 'straight-line approximation'. This restriction is removed in the present paper. A 'hyperbolical approximation' of the impedance function z(x) is introduced and it is shown that with this function the two-dimensional cochlea model can be solved in closed form. The computation results show that, for not too large values of the damping parameter delta, the response in the neighbourhood of the resonance location is almost as well represented by the formerly used 'straight-line approximation' as by the 'hyperbolic approximation'. Hence the principal aspects of cochlear resonance are well brought to light with the 'straight-line approximation'. This implies that in the case under consideration the dominant part played by short waves is confirmed. When a larger range of x values is to be considered, the hyperbolic approximation is advantageous. The computed response functions agree better with experimental data from the literature. However, it is clear that really satisfactory agreement seems not possible with a two-dimensional model.

Basilar Membrane↗
PubMed1980

A cylindrical cochlea model: the bridge between two and three dimensions.

In this paper the response is studied of a linear two-channel of the cochlea with a circular cross-section. In conformity with anatomical data the basilar membrane occupies only a small fraction of the width of the cochlear partition separating the channels. Fluid displaced by the membrane will move mainly in the longitudinal (x) direction, the remainder is assumed to occur only in the radial (r) direction. In this way the major effect of three-dimensional fluid movement is built in, yet the mathematical treatment can proceed as in two-dimensional theory. The problem can be solved by analytical means when the membrane is taken as completely described by the mechanical impedance z(x) and the functional form of z(x) is simplified to a sufficient degree. Near the locus of resonance z(x) is nearly a linear function of x. For this case - the straight-line approximation of z(x) - the solution of the problem is straightforward. The response of this three-dimensional model is found to have characteristics about midway between those of one- and two-dimensional models. The same general properties are found when a better approximation - the hyperbolic approximation - of z(x) is introduced. In the resonance region the computed response for this model agrees excellently with experimental data, much better than for a two-dimensional model. A noteworthy feature of the three-dimensional response is that in the resonance region the response is well elevated above its course in the remainder of the cochlea (where wave propagation can be regarded as one-dimensional model). In this respect the three-dimensional response differs fundamentally from that of the two-dimensional model. This property is also found in certain experimental data, and from the present results this feature can be interpreted as specific for a three-dimensional structure. Further work should be directed at other three-dimensional structures in which the basilar membrane also occupies a small fraction of the width of the cochlear partition, and at more elaborate types of model.

Basilar Membrane↗
PubMed1980

Short and long waves in the cochlea.

Mathematically, it is attractive to model cochlear dynamics as a one-dimensional problem. This implies the hypothesis that the (smallest) wavelength is large compared to the cross-section of the cochlear channels. It is suspected that this hypothesis is not justified at and near the place where the wavelength is smallest. For several types of model the response is computed with due allowance for short waves. The results show that in the pertinent region short waves completely dominate the response. Several consequences of this finding are discussed.

Basilar Membrane↗
PubMed1980

Nonlinear interactions and the 'Kemp echo'.

It would be convenient to assume one nonlinear interaction process as responsible for almost all cochlear nonlinearities including the 'Kemp echo'. In this paper various possible forms of such a process are discussed. In general the interaction assumes the form of a feedback system, its input being derived from physiological excitation and its output affecting the propagation of cochlear waves. Only first-harmonic effects are considered here. If the feedback derives from the averaged physiological activity, it effectively modifies cochlear mechanics. In the modeling exercises it proved impossible to construct a feedback system that would have the largest effects near the location of resonance, hence with this type of feedback system the desired goal cannot be attained. In another form the feedback signal is considered to be a variable that directly relates to physiological excitation, an intracellular potential, for instance. This type of feedback operates strictly locally. The functional forms of sharpened responses and (short-wave) cochlear mechanics are fairly well known, and the feedback system can be implemented rather easily. The results were somewhat unexpected: the resulting system has an innate tendency to be unstable. It seems that the types of feedback systems considered cannot be regarded as likely candidates for a nonlinear theory of the cochlea.

Biomechanical Phenomena↗
PubMed1980

Reflections on reflections.

Most cochlea models consider the system as a pair of channels separated by a flexible membrane (basilar membrane). In the part of the wave where the stiffness of the membrane dominates, traveling waves are set up. Because of varying propagation conditions the speed of propagation diminishes most rapidly when the wave approaches the region where the basilar membrane shows resonance for the frequency under consideration. It might be expected that such a rapid change of propagation velocity gives rise to reflection. In this paper a one-dimensional model is considered in such a way that resonance properties stand out clearly. The results show that even when extremely little damping occurs (damping factor less than 10(-3)) virtually no reflection is evident. under conditions of low damping the nature of the response is such that it is incompatible with inner hair cell or nerve fiber responses from the cochlea: some kind of "sharpening mechanism" should be present. Limitations of the model considered should be studied further to verify the conclusions in more general cases. Despite these limitations the present model serves to illustrate typical physical phenomena, like reflection and energy dissipation, quite well.

Basilar Membrane↗
PubMed1979

The structure of the human beta-globin gene in beta-thalassaemia.

Twenty-one cases of beta 0 and beta +-thalassaemia have been analysed by restriction endonuclease mapping. In most cases no deletion in the regions surrounding the beta- and delta-globin genes could be detected. However, in a single Asian case of beta 0-thalassaemia, homozygous clinically, one of the homologous chromosomes contained a beta-globin gene with a deletion of 600 base pairs of DNA and comprising most or all of the 3' end of the structural gene including the EcoRI restriction site within the beta-globin coding sequence.

DNA↗
PubMed1975

Clinical psychophysics. Illustrated by the problem of auditory overload.

In some patients with sensorineural hearing loss, masking extends over an abnormally wide range toward the higher frequencies. Most likely the main determinant is excessive harmonic distortion. Under this assumption, the masking measured with a probe tone at 2 kHz, due to a masker tone of 1 kHz, should be dependent upon the phase of the probe tone. This has been confirmed experimentally; it proved possible to derive the strength and phase of the equivalent second harmonic from the data. For normal ears, the strength was found to depend upon the SPL of the masker in the expected, quadratic manner. The phase was found to exhibit a startlingly rapid transition over nearly 360 degrees within one octave (500-1 000 Hz fundamental). Results of clinical measurements with the same method will be discussed.

Acoustic Stimulation↗