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P van Dijk

Publications and source records attributed to P van Dijk.

At least 55 records · Page 3Linked to original sources

Singlet oxygen-induced DNA damage: product analysis, studies of biological consequences and characterization of mutations.

The DNA lesions induced by free 1O2 and the biological and mutagenic consequences of 1O2-induced DNA damage have been studied. Using anion exchange HPLC, reverse-phase HPLC with electrochemical detection and 32P-postlabelling methods, we have shown that 1O2 reacts with 2'-deoxyguanine 3'-monophosphate (dGp) but not with any other dNp. Reaction with dGp yields a large number of products; one minor product was identified as 7-hydro-8-oxo-2'-deoxyguanosine 3'-monophosphate (8-oxo-dGp), and a second tentatively as a formamidopyridine derivative of dGp. 8-Oxo-dGp was also found after reaction of 1O2 with single-stranded (ss) DNA, double-stranded (ds) DNA or an oligonucleotide (16-mer) having one G. With the oligonucleotide we found a second unidentified reaction product. With ss DNA, 8-oxo-dG was a much more prominent product than in the reaction of 1O2 with free dGp and the yield was about eight-fold higher than with ds DNA. This agrees with our finding that ss M13 DNA is at least 100-fold more sensitive than ds M13 DNA to biological inactivation by 1O2. The inactivation of ss M13 DNA must be largely due to 1O2-induced lesions other than 8-oxo-dG. In agreement with the observed preferential reaction of 1O2 with dG, most of the mutations induced by 1O2 in ss or ds M13mp10 DNA occurred at a G or G/C basepair, respectively. A preference for G(C) to T(A) transversions was observed for which 8-oxo-dG might have been responsible. In ss DNA, a significant number of mutations are characterized by the fact that a G is deleted.

Bacteriophage M13↗

Interaction of singlet oxygen with DNA and biological consequences.

To study the interaction of singlet oxygen (1O2) with DNA and the biological consequences of 1O2-induced DNA damage, we used the thermodissociable endoperoxide of 3,3'-(1,4 naphthalidene) dipropionate (NDPO2) as a generator of free 1O2 in reactions with (1) 2'-deoxynucleoside 3'-monophosphates (dNps), (2) an oligonucleotide (16-mer) having one deoxyguanine (dG), (3) native and denaturated rat kidney DNA and (4) single-stranded (ss) and double-stranded (ds) bacteriophage M13mp10 DNA. Using both anion exchange and reversed phase HPLC and 32P-postlabeling analyses, it was found that exposure of the various dNps to chemically generated 1O2 led to a detectable reaction with dGp and not with dAp, dCp, d5mCp or Tp. The reaction with dGp led to degradation of this nucleotide and the formation of a large number of reaction products, one of which could be identified as 7-hydro-8-oxo-2'-deoxyguanosine 3'-monophosphate (8-oxo-dGp). A second product could tentatively be identified as a formamido pyrimidine derivative of dGp (Fapy-dGp). When ss DNA, ds DNA or the oligonucleotide were exposed to 1O2, the formation of 8-oxo-dG could also be demonstrated. With the oligonucleotide, we found a so far unidentified reaction product. Under the same reaction conditions the yield of 8-oxo-dG was about 8-fold higher in ss DNA than in ds DNA. In ss DNA 8-oxo-dG seemed to be a more prominent product than in the case of reaction of 1O2 with free dGp. Reaction of 1O2 with ss or ds M13mp10 DNA led to biological inactivation of these DNAs, ss DNA being at least 100-fold more sensitive than ds DNA. It could be concluded that inactivation of the ss DNA must be largely due to 1O2-induced DNA lesions other than 8-oxo-dG. In agreement with the observed preferential reaction of 1O2 with dG most of the so far sequenced mutations, induced by 1O2 in a 144 bp mutation target sequence inserted in the lacZ alpha gene of ss or ds M13mp10 DNA, occurred at a G or G/C base pair respectively. A preference for G(C) to T(A) transversions can be observed for which 8-oxo-dG might have been responsible. In ss DNA a significant number of the mutations are characterized by the fact that a G is deleted.

Animals↗

[Experimental studies on magnetic resonance tomographic and magnetic resonance angiographic imaging of poststenotic flow patterns].

A phantom has been developed, which permits the perfusion of defined stenosis with variable flow rates. The post-stenotic flow patterns were imaged by means of conventional MRI sequences and special angiographic sequences using a 1.5 total body scanner (Gyroscan S15, Philips). For conventional MRI images, spin-echo-sequences (TR 500 ms, TE 27 ms with reconstruction of the magnitude and phase images) and gradient-echo-sequences (TR 60 ms, TE 27 ms, flip angle 15 degrees with reconstruction of the magnitude images) were used. For MR angiography 2D inflow (multiple-single-slice-technique, TR 40 ms, TE 14 ms, flip angle 60 degrees) and flow-adjusted-gradient-sequences (TR 24 ms, TE 10 ms, flip angle 60 degrees) were performed. In addition to an analysis of the appearances, the length of the changed signal intensity beyond the stenosis was evaluated. For constant flow rates it increases with the severity of the stenosis. For a constant stenosis the length of the post-stenotic signal change alters with flow rate. The changes also depend on the direction of flow and the gradients of the chosen sequences. The comparison of magnitude and phase images allows the discrimination between turbulent and non-turbulent flow. It therefore appears possible to estimate the severity of arteriosclerotic occlusive disease by means of MRI in the future.

Blood Flow Velocity↗

[Monitoring of the oxygen saturation of horses during halothane anesthesia using pulse oximetry in the nasal septum].

The use of pulse oximetry for on-line monitoring of oxygen saturation of arterial blood using a probe on the nasal septum is described in the horse. When compared to the results of blood gas analysis an excellent correlation between the two methods for measuring oxygen saturation is found. Nevertheless a discrepancy between the values for oxygen saturation provided by either method is found. This can lead to misinterpretation of oxygen saturation values generated by the pulse oximeter. The cause of this discrepancy is not clear but differences in measuring principle, presence of dyshemoglobins and differences in absorption characteristics of hemoglobin are to be ruled out as major contributors. Contrary to findings in several other animal species occasionally double counting of pulse frequency by the pulse oximeter is seen.

Anesthesia↗

Temperature effects on auditory nerve fiber response in the American bullfrog.

Single fiber recordings were made from auditory nerve fibers of the American bullfrog (Rana catesbeiana). As temperature was raised: (1) Best frequencies of fibers from the amphibian papilla (N = 15) increased. Below 600 Hz best frequency changes up to 0.06 oct/degrees C were found; above 600 Hz changes were less than 0.03 oct/degrees C. In the basilar papilla (N = 4) no significant increase of best frequency was found. (2) Spike rates in response to fixed-RMS-amplitude stimuli increased considerably: Q10 of spike rate ranged from 5 to 10. (3) Spontaneous activity, found in basilar papilla fibers, increased with average Q10 = 1.6 (+/- 0.3). (4) A conspicuous change of tuning quality factor Q10 dB was only observed in two fibers, that were taken to low temperatures (less than 16 degrees C). (5) the nearly linear frequency vs. phase relation in amphibian papilla shifts to higher frequency (along with shift of best frequency), while its average slope remains nearly unchanged.

Action Potentials↗

Synchronization of spontaneous otoacoustic emissions to a 2f1-f2 distortion product.

Synchronization of spontaneous otoacoustic emissions to a cubic distortion frequency fs = 2f1-f2 has been studied. Stimulus, consisting of two primary tones at frequency f1 and f2, could easily be filtered out of the microphone signal. This enabled us to monitor emission phase with respect to synchronization frequency fs, by recording zero-crossing moments of the microphone signal. When primaries were sufficiently loud (typically 30 dB SPL), phase fluctuated around a constant value: The emission was constantly synchronized to fs. Lowering primary levels (to typically 20 dB SPL) resulted in 2 pi-phase jumps at random moments: The emission occasionally slipped out of synchronization, trying to maintain its own natural frequency f0. This behavior can be described as synchronization of an oscillator (frequency f0) to a sinusoidal force (frequency fs) in the presence of noise.

Auditory Threshold↗

Amplitude and frequency fluctuations of spontaneous otoacoustic emissions.

Amplitude and frequency fluctuations of spontaneous otoacoustic emissions have been studied. Spontaneous otoacoustic emissions were recorded from eight human ears and two frog ears (Rana esculenta). Record length typically was 80 s. For a recorded emission signal, the amplitude signal A(t) (average A0) and time intervals T(ti) between successive positive-going zero crossings (i counts zero crossings) were determined. Emission amplitude and period both showed small fluctuations: delta Arms/A0 ranged from 0.7 X 10(-2) to 6.3 X 10(-2) for human emissions and was 24 X 10(-2) for both frog emissions; delta Trms ranged from 1.4 to 6.9 X 10(-7) s for human emission and was 50.0 and 55.0 X 10(-7) s for the two frog emissions. There was a positive correlation between delta Arms/A0 and delta Trms as determined for different emissions (R = 0.9). Spectra of A(t) and T(ti) revealed that amplitude and period were slowly fluctuating functions: cutoff frequency delta f delta A of the amplitude spectrum ranged from 3 to 18 Hz; delta f delta T ranged from 7 to 32 Hz. Results have been compared to amplitude and frequency fluctuations of a second-order oscillator, that interacts with a noise source. It has been concluded that an oscillator with linear stiffness (for example a Van der Pol oscillator) driven by white Gaussian noise, cannot account for all experimental results. Other possible oscillators (e.g., nonlinear stiffness) and noise sources (e.g., narrow-band noise), that may account for the observed phenomena, are discussed.

Animals↗

Assignment of seven genes to distinct intervals on the midportion of human chromosome 19q surrounding the myotonic dystrophy gene region.

Hybridization studies using a panel of somatic cell hybrids with subchromosomal segments of 19q have localized the genes encoding hormone-sensitive lipase (LIPE), carcinoembryonic antigen (CEA), and small nuclear ribonucleoprotein polypeptide A (SNRPA) to various regions of 19q13.1; the cellular receptor for poliovirus sensitivity (PVS) to 19q13.2; and the genes coding for prostate-specific antigen (APS), human pancreatic kallikrein (KLK1), and small nuclear ribonucleoprotein 70-kD polypeptide (SNRP70) to 19q13.3----qter. Our results exclude several of these genes from being seriously considered as a candidate for the myotonic dystrophy gene on 19q.

Animals↗

DC injection alters spontaneous otoacoustic emission frequency in the frog.

A permanent wire electrode was implanted in the inner ear of the green frog (Rana esculenta). Through this electrode direct current was delivered to the inner ear fluid of the frog, during recording of a spontaneous otoacoustic emission (SOAE). Both SOAE frequency and amplitude turned out to depend on DC level and polarity. Possible explanations for the observed phenomena are given, based on a dissipative limit-cycle oscillator model for SOAE generation, and the assumption that SOAE frequency depends on hair cell ion channel inductance.

Animals↗

Spontaneous otoacoustic emissions in the European edible frog (Rana esculenta): spectral details and temperature dependence.

Spontaneous otoacoustic emissions were recorded in 41 ears of 29 European edible frogs (Rana esculenta). Emission frequencies ranged from 450 to 1350 Hz. The distribution of frequencies shows two distinct populations: one above and one below 1 kHz. With one exception, a maximum number of two emissions were recorded per ear, each in a different population. An amplitude distribution of a frog emission was sampled, from which it was concluded that the emission is generated by an active oscillator. The spectral width of an emission ranged from 1 to 200 Hz (average 38 Hz). There was negative correlation between sound pressure level of an emission and spectral width. In 4 frogs the dependence of emission power and frequency on temperature was investigated. An emission could be 'switched on and off' within a few degrees centigrade. At temperatures below the switching interval no emission was recorded; for higher temperatures emission power showed no dependence on temperature. Frequency increased with temperature (Q10 = 1.1 to 1.3). This yields a mismatch with temperature dependence of best frequencies of auditory fibers. The consequences of this mismatch are discussed.

Animals↗

Synthesis of heterocyclic N-acetoxyarylamines and their reactivity with DNA.

2-Acetoxyamino-5-phenylpyridine and 2-acetoxyamino-3-methyl-5-phenylpyridine, being proposed ultimate carcinogens of the heterocyclic aromatic amines 2-amino-5-phenylpyridine (APP) and 2-amino-3-methyl-5-phenylpyridine (AMPP), respectively, were synthesized, crystallized and characterized. Using the 32P-postlabelling technique, we show that the total amount of adducts found in DNA after reaction with these N-acetoxyarylamines is at least 30- and 450-fold higher than in DNA reacted with equimolar amounts of the proposed proximate carcinogens 2-hydroxyamino-5-phenylpyridine and 2-hydroxyamino-3-methyl-5-phenylpyridine, respectively. These results support a postulated activation mechanism, in which N-acetoxyarylamines are the ultimate reactive species responsible for DNA modification by carcinogenic aromatic amines in vivo. The possibility to obtain the reactive 0-acetyl derivatives of APP and AMPP in crystalline form makes them unique model compounds for studies on the interaction of ultimate carcinogens of aromatic amines with DNA.

Amines↗

Magnetic resonance imaging of the cerebral aqueduct. Signal intensity time curves demonstrated by fast acquisition with multiple excitation (FAME).

Using cardiac-gated fast acquisition with multiple excitation (FAME), time curves of the cerebral aqueduct signals were derived in 19 healthy volunteers and 14 patients. A mean curve of the normal subjects was determined during systole. A relatively stable point of time was found at 270 msec after the R-wave supposed to be the reversal of the flow of cerebral-spinal fluid in the aqueduct. Different curves were noticed in complete aqueductal obstruction (n = 2); in other pathologic states, such as cerebral tumor (n = 3), normal pressure hydrocephalus (n = 3), and brain atrophy (n = 1), no different signal time curves were observed. Parameters such as aqueduct diameter, cerebro-spinal fluid volume and brain compliance are probably other important factors in aqueduct liquor flow.

Adolescent↗

Regional localization of the gene encoding pregnancy specific beta-1-glycoprotein 1 (PSBG1) to human chromosome 19q13.1.

Pregnancy specific beta-1-glycoprotein (PSBG), a major product of the human placenta, is encoded by multiple genes. Southern blot hybridization of human x rodent somatic cell hybrid DNAs with a cDNA specific for one member of the PSBG gene family allowed us to map this gene to human chromosome 19. Further analysis using hybrids with subchromosomal segments of 19q revealed that the gene maps to the distal segment of region 19q13.1.

Animals↗

Multi-exponential relaxation analysis with MR imaging and NMR spectroscopy using fat-water systems.

This study was undertaken to evaluate the feasibility of multiexponential relaxation data analysis to MR imaging techniques. The first part of this study contains accurate relaxation time measurements performed on a conventional spectrometer. In the second part, essentially the same measuring techniques were applied but now on standard whole body MR imaging equipment. T2 relaxation was measured using multi-echo techniques, T1 relaxation using multiple inversion recovery measurements. Manganese chloride solutions were used for verification of the single exponential model. Water and fat mixtures were considered for multi-exponentiality. Pure fat showed an intrinsic two-exponentiality in T1 and T2 relaxation. Mixtures of fat and water were analyzed and could at best be characterized by two exponentials, although at least three exponentials were known to be present. From the two-exponential fit the relative amounts of fat and water were calculated and compared with the mixture composition. Statistical criteria are discussed to discriminate between single and double exponential behavior in relaxation curves. It is concluded that the time consuming IR measurements for the determination of multiple T1 relaxation are not applicable in a clinical environment. Multiple T2 relaxation can be determined in a reasonable amount of time using multiple echo measurements in one image acquisition. It is shown that the observed values of T1 and T2 from tissues with intrinsic multiexponential relaxation behavior, measured with MR imaging or MR relaxation techniques on a whole-body imager or a conventional spectrometer, depend strongly on the way the experiments are set up and on the model accepted for data analysis.

Fats↗

Clinical, cardiovascular and respiratory effects of R8110 in premedicated dogs.

The clinical, cardiovascular and respiratory effects after i.v. administration of R8110, a fluoro analogue of etomidate (Fig. 1), were studied in pre-medicated dogs. The clinical observations were made at doses of 3 and 4 mg/kg body weight (BW) injected slowly i.v., whereas cardiovascular and respiratory studies were carried out at a dose rate of 3 mg/kg R8110 i.v. Induction and recovery were smooth and no significant side-effects were observed. The cardiovascular system was slightly influenced, but respiration was hardly affected. The effect of pre-medication on respiration and the cardiovascular system was hardly potentiated by R8110. Although there were significant changes in cardiovascular and biochemical parameters, all values remained within physiological limits. R8110 appeared to be a safe and reliable induction agent.

Acepromazine↗